• dr Piotr Siupka
Stanowisko: Adiunkt
Jednostka: Wydział Nauk Przyrodniczych
Adres: 40-032 Katowice, ul. Jagiellońska 28
Piętro: parter
Numer pokoju: A-39
Telefon: (32) 2009 359
E-mail: piotr.siupka@us.edu.pl
Spis publikacji: Spis wg CINiBA
Spis publikacji: Spis wg OPUS
Scopus Author ID: 49864411900
Publikacje z bazy Scopus
2022
Nádudvari, Á.; Cabała, J.; Marynowski, L.; Jabłońska, M.; Dziurowicz, M.; Malczewski, D.; Kozielska, B.; Siupka, P.; Piotrowska-Seget, Z.; Simoneit, B. R. T.; Szczyrba, M.
High concentrations of HgS, MeHg and toxic gas emissions in thermally affected waste dumps from hard coal mining in Poland Journal Article
In: Journal of Hazardous Materials, vol. 431, 2022, ISSN: 03043894, (4).
@article{2-s2.0-85125539700,
title = {High concentrations of HgS, MeHg and toxic gas emissions in thermally affected waste dumps from hard coal mining in Poland},
author = { Á. Nádudvari and J. Cabała and L. Marynowski and M. Jabłońska and M. Dziurowicz and D. Malczewski and B. Kozielska and P. Siupka and Z. Piotrowska-Seget and B.R.T. Simoneit and M. Szczyrba},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85125539700&doi=10.1016%2fj.jhazmat.2022.128542&partnerID=40&md5=dc4d622cf940b6c3ae23b6a2bebc9f65},
doi = {10.1016/j.jhazmat.2022.128542},
issn = {03043894},
year = {2022},
date = {2022-01-01},
journal = {Journal of Hazardous Materials},
volume = {431},
publisher = {Elsevier B.V.},
abstract = {This study aims to provide numerous environmental research approaches to understand the formation of mineral and organic mercury compounds in self-heating coal waste dumps of the Upper Silesian Coal Basin (USCB). The results are combined with environmental and health risk assessments. The mineralogy comprised accessory minerals in the fine fraction of thermally affected waste, i.e., Hg sulfides, most likely cinnabar or metacinnabar. Moreover, other metals, e.g., Pb, Zn and Cu, were found as sulfide forms. Apart from Hg, the ICP-ES/MS data confirmed the high content of Mn, Zn, Pb, Hg, Cr and Ba in these wastes. The high concentration of available Hg resulted in elevated MeHg concentrations in the dumps. There were no correlations or trends between MeHg concentrations and elemental Hg, TS, TOC, and pH. Furthermore, we did not detect microbial genes responsible for Hg methylation. The organic compounds identified in waste and emitted gases, such as organic acids, or free methyl radicals, common in such burn environments, could be responsible for the formation of MeHg. The concentration levels of gases, e.g., benzene, formaldehyde, NH3, emitted by the vents, reached or surpassed acceptable levels numerous times. The potential ecological and human health risks of these dumps were moderate to very high due to the significant influence of the high Hg concentrations. © 2022 Elsevier B.V.},
note = {4},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2021
Krain, A.; Siupka, P.
Fungal guttation, a source of bioactive compounds and its ecological role—a review Journal Article
In: Biomolecules, vol. 11, no. 9, 2021, ISSN: 2218273X, (5).
@article{2-s2.0-85113350084,
title = {Fungal guttation, a source of bioactive compounds and its ecological role—a review},
author = { A. Krain and P. Siupka},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85113350084&doi=10.3390%2fbiom11091270&partnerID=40&md5=4628a6a5bf43b9e6b9c5e427a60425f8},
doi = {10.3390/biom11091270},
issn = {2218273X},
year = {2021},
date = {2021-01-01},
journal = {Biomolecules},
volume = {11},
number = {9},
publisher = {MDPI AG},
abstract = {Guttation is a common phenomenon in the fungal kingdom. Its occurrence and intensity depend largely on culture conditions, such as growth medium composition or incubation temperature. As filamentous fungi are a rich source of compounds, possessing various biological activities, guttation exudates could also contain bioactive substances. Among such molecules, researchers have already found numerous mycotoxins, antimicrobials, insecticides, bioherbicides, antiviral, and anticancer agents in exudate droplets. They belong to either secondary metabolites (SMs) or proteins and are secreted with different intensities. The background of guttation, in terms of its biological role, in vivo, and promoting factors, has been explored only partially. In this review, we describe the metabolites present in fungal exudates, their diversity, and bioactivities. Pointing to the significance of fungal ecology and natural products discovery, selected aspects of guttation in the fungi are discussed. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.},
note = {5},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Siupka, P.; Hansen, F. T.; Schier, A.; Rocco, S.; Sørensen, T.; Piotrowska-Seget, Z.
Antifungal activity and biosynthetic potential of new streptomyces sp. MW-W600-10 strain isolated from coal mine water Journal Article
In: International Journal of Molecular Sciences, vol. 22, no. 14, 2021, ISSN: 16616596, (2).
@article{2-s2.0-85109547295,
title = {Antifungal activity and biosynthetic potential of new streptomyces sp. MW-W600-10 strain isolated from coal mine water},
author = { P. Siupka and F.T. Hansen and A. Schier and S. Rocco and T. Sørensen and Z. Piotrowska-Seget},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85109547295&doi=10.3390%2fijms22147441&partnerID=40&md5=13775f8fa8f0c93edaeabb59cf4538e2},
doi = {10.3390/ijms22147441},
issn = {16616596},
year = {2021},
date = {2021-01-01},
journal = {International Journal of Molecular Sciences},
volume = {22},
number = {14},
publisher = {MDPI AG},
abstract = {Crop infections by fungi lead to severe losses in food production and pose risks for human health. The increasing resistance of pathogens to fungicides has led to the higher usage of these chemicals, which burdens the environment and highlights the need to find novel natural biocontrol agents. Members of the genus Streptomyces are known to produce a plethora of bioactive compounds. Recently, researchers have turned to extreme and previously unexplored niches in the search for new strains with antimicrobial activities. One such niche are underground coal mine environments. We isolated the new Streptomyces sp. MW-W600-10 strain from coal mine water samples collected at 665 m below ground level. We examined the antifungal activity of the strain against plant pathogens Fusarium culmorum DSM62188 and Nigrospora oryzae roseF7. Furthermore, we analyzed the strain’s biosynthetic potential with the antiSMASH tool. The strain showed inhibitory activity against both fungi strains. Genome mining revealed that it has 39 BGCs, among which 13 did not show similarity to those in databases. Additionally, we examined the activity of the Streptomyces sp. S-2 strain isolated from black soot against F. culmorum DSM62188. These results show that coal-related strains could be a source of novel bioactive compounds. Future studies will elucidate their full biotechnological potential. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.},
note = {2},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2020
Amoushahi, M.; Steffensen, L. L.; Galieva, A.; Agger, J.; Heuck, A.; Siupka, P.; Ernst, E.; Nielsen, M. S.; Sunde, L.; Lykke-Hartmann, K.
Maternally contributed Nlrp9b expressed in human and mouse ovarian follicles contributes to early murine preimplantation development Journal Article
In: Journal of Assisted Reproduction and Genetics, vol. 37, no. 6, pp. 1355-1365, 2020, ISSN: 10580468, (1).
@article{2-s2.0-85084679950,
title = {Maternally contributed Nlrp9b expressed in human and mouse ovarian follicles contributes to early murine preimplantation development},
author = { M. Amoushahi and L.L. Steffensen and A. Galieva and J. Agger and A. Heuck and P. Siupka and E. Ernst and M.S. Nielsen and L. Sunde and K. Lykke-Hartmann},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084679950&doi=10.1007%2fs10815-020-01767-w&partnerID=40&md5=6b3739e2b1ab8d14d3cfbcca152c3ae0},
doi = {10.1007/s10815-020-01767-w},
issn = {10580468},
year = {2020},
date = {2020-01-01},
journal = {Journal of Assisted Reproduction and Genetics},
volume = {37},
number = {6},
pages = {1355-1365},
publisher = {Springer},
abstract = {Purpose: The aim of the study is to investigate presence and role of the gene encoding the maternally contributed nucleotide-binding oligomerization domain (NOD)–like receptors with a pyrin domain (PYD)–containing protein 9 (NLRP9) in human and mouse ovaries, respectively, and in preimplantation mouse embryo development by knocking down Nlrp9b. Methods: Expression levels of NLRP9 mRNA in human follicles were extracted from RNA sequencing data from previous studies. In this study, we performed a qPCR analysis of Nlpr9b mRNA in mouse oocytes and found it present. Intracellular ovarian distribution of NLRP9B protein was accomplished using immunohistochemistry. The distribution of NLRP9B was explored using a reporter gene approach, fusing NLRP9B to green fluorescent protein and microinjection of in vitro–generated mRNA. Nlrp9b mRNA function was knocked down by microinjection of short interference (si) RNA targeting Nlrp9b, into mouse pronuclear zygotes. Knockdown of the Nlrp9b mRNA transcript was confirmed by qPCR. Result: We found that the human NLRP9 gene and its corresponding protein are highly expressed in human primordial and primary follicles. The NLRP9B protein is localized to the cytoplasm in the blastomeres of a 2-cell embryo in mice. SiRNA-mediated knockdown of Nlrp9b caused rapid elimination of endogenous Nlrp9b mRNA and premature embryo arrest at the 2- to 4-cell stages compared with that of the siRNA-scrambled control group. Conclusions: These results suggest that mouse Nlrp9b, as a maternal effect gene, could contribute to mouse preimplantation embryo development. It remains to investigate whether NLRP9 have a crucial role in human preimplantation embryo and infertility. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.},
note = {1},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Siupka, P.; Piński, A.; Babicka, D.; Piotrowska-Seget, Z.
Genome mining revealed a high biosynthetic potential for antifungal streptomyces sp. S-2 isolated from black soot Journal Article
In: International Journal of Molecular Sciences, vol. 21, no. 7, 2020, ISSN: 16616596, (4).
@article{2-s2.0-85083227042,
title = {Genome mining revealed a high biosynthetic potential for antifungal streptomyces sp. S-2 isolated from black soot},
author = { P. Siupka and A. Piński and D. Babicka and Z. Piotrowska-Seget},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083227042&doi=10.3390%2fijms21072558&partnerID=40&md5=8d03614905f0d09dac5423ffa3cca837},
doi = {10.3390/ijms21072558},
issn = {16616596},
year = {2020},
date = {2020-01-01},
journal = {International Journal of Molecular Sciences},
volume = {21},
number = {7},
publisher = {MDPI AG},
abstract = {The increasing resistance of fungal pathogens has heightened the necessity of searching for new organisms and compounds to combat their spread. Streptomyces are bacteria that are well-known for the production of many antibiotics. To find novel antibiotic agents, researchers have turned to previously neglected and extreme environments. Here, we isolated a new strain, Streptomyces sp. S-2, for the first time, from black soot after hard coal combustion (collected from an in-use household chimney). We examined its antifungal properties against plant pathogens and against fungi that potentially pose threat to human health (Fusarium avenaceum; Aspergillus niger and the environmental isolates Trichoderma citrinoviridae Cin-9; Nigrospora oryzae sp. roseF7; and Curvularia coatesieae sp. junF9). Furthermore, we obtained the genome sequence of S-2 and examined its potential for secondary metabolites production using anti-SMASH software. The S-2 strain shows activity against all of the tested fungi. Genome mining elucidated a vast number of biosynthetic gene clusters (55), which distinguish this strain from closely related strains. The majority of the predicted clusters were assigned to non-ribosomal peptide synthetases or type 1 polyketide synthetases, groups known to produce compounds with antimicrobial activity. A high number of the gene clusters showed no, or low similarity to those in the database, raising the possibility that S-2 could be a producer of novel antibiotics. Future studies on Streptomyces sp. S-2 will elucidate its full biotechnological potential. © 2020 by the authors.},
note = {4},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2019
Madsen, P.; Isaksen, T. J.; Siupka, P.; Tóth, A. E.; Nyegaard, M.; Gustafsen, C.; Nielsen, M. S.
HSPA12A targets the cytoplasmic domain and affects the trafficking of the Amyloid Precursor Protein receptor SorLA Journal Article
In: Scientific Reports, vol. 9, no. 1, 2019, ISSN: 20452322, (4).
@article{2-s2.0-85060526147,
title = {HSPA12A targets the cytoplasmic domain and affects the trafficking of the Amyloid Precursor Protein receptor SorLA},
author = { P. Madsen and T.J. Isaksen and P. Siupka and A.E. Tóth and M. Nyegaard and C. Gustafsen and M.S. Nielsen},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060526147&doi=10.1038%2fs41598-018-37336-6&partnerID=40&md5=dcf82a3ea5ae554fceb3f7e157dbed08},
doi = {10.1038/s41598-018-37336-6},
issn = {20452322},
year = {2019},
date = {2019-01-01},
journal = {Scientific Reports},
volume = {9},
number = {1},
publisher = {Nature Publishing Group},
abstract = {SorLA and Sortilin are multifunctional receptors involved in endocytosis and intracellular sorting of different and unrelated ligands. SorLA has recently attracted much attention as a novel strong risk gene for Alzheimer’s disease, and much effort is currently being put into understanding the underlying molecular mechanism. Trafficking of SorLA and Sortilin are mediated by interacting with AP-1, AP-2, GGA 1-3 and the retromer complex. Although these cytosolic adaptor proteins all bind to both SorLA and Sortilin, a large fraction of intracellular Sortilin and SorLA are located in different subcellular vesicles. This indicates that unknown specialised adaptor proteins targeting SorLA for trafficking are yet to be discovered. We have identified HSPA12A as a new adaptor protein that, among Vps10p-D receptors, selectively binds to SorLA in an ADP/ATP dependent manner. This is the first described substrate of HSPA12A, and we demonstrate that the binding, which affects both endocytic speed and subcellular localisation of SorLA, is mediated by specific acidic residues in the cytosolic domain of SorLA. The identification of the relatively unknown HSPA12A as a SorLA specific interaction partner could lead to novel insight into the molecular mechanism of SorLA, and re-emphasises the role of heat shock proteins in neurodegenerative diseases. © 2019, The Author(s).},
note = {4},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2018
Tóth, A. E.; Siupka, P.; Augustine, T. J. P.; Venø, S. T.; Thomsen, L. B.; Moos, T.; Lohi, H. T.; Madsen, P.; Lykke-Hartmann, K.; Nielsen, M. S.
The Endo-Lysosomal System of Brain Endothelial Cells Is Influenced by Astrocytes In Vitro Journal Article
In: Molecular Neurobiology, vol. 55, no. 11, pp. 8522-8537, 2018, ISSN: 08937648, (10).
@article{2-s2.0-85046007831,
title = {The Endo-Lysosomal System of Brain Endothelial Cells Is Influenced by Astrocytes In Vitro},
author = { A.E. Tóth and P. Siupka and T.J. P. Augustine and S.T. Venø and L.B. Thomsen and T. Moos and H.T. Lohi and P. Madsen and K. Lykke-Hartmann and M.S. Nielsen},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046007831&doi=10.1007%2fs12035-018-0988-x&partnerID=40&md5=560eaec31ad27888132f325002663f75},
doi = {10.1007/s12035-018-0988-x},
issn = {08937648},
year = {2018},
date = {2018-01-01},
journal = {Molecular Neurobiology},
volume = {55},
number = {11},
pages = {8522-8537},
publisher = {Humana Press Inc.},
abstract = {Receptor- and adsorptive-mediated transport through brain endothelial cells (BEC) of the blood-brain barrier (BBB) involves a complex array of subcellular vesicular structures, the endo-lysosomal system. It consists of several types of vesicles, such as early, recycling, and late endosomes, retromer-positive structures, and lysosomes. Since this system is important for receptor-mediated transcytosis of drugs across brain capillaries, our aim was to characterise the endo-lysosomal system in BEC with emphasis on their interactions with astrocytes. We used primary porcine BEC in monoculture and in co-culture with primary rat astrocytes. The presence of astrocytes changed the intraendothelial vesicular network and significantly impacted vesicular number, morphology, and distribution. Additionally, gene set enrichment analysis revealed that 60 genes associated with vesicular trafficking showed altered expression in co-cultured BEC. Cytosolic proteins involved in subcellular trafficking were investigated to mark transport routes, such as RAB25 for transcytosis. Strikingly, the adaptor protein called AP1-μ1B, important for basolateral sorting in epithelial cells, was not expressed in BEC. Altogether, our data pin-point unique features of BEC trafficking network, essentially mapping the endo-lysosomal system of in vitro BBB models. Consequently, our findings constitute a valuable basis for planning the optimal route across the BBB when advancing drug delivery to the brain. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.},
note = {10},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2017
Johnsen, K. B.; Burkhart, A.; Melander, F.; Kempen, P. J.; Vejlebo, J. B.; Siupka, P.; Nielsen, M. S.; Andresen, T. L.; Moos, T.
In: Scientific Reports, vol. 7, no. 1, 2017, ISSN: 20452322, (114).
@article{2-s2.0-85028842976,
title = {Targeting transferrin receptors at the blood-brain barrier improves the uptake of immunoliposomes and subsequent cargo transport into the brain parenchyma},
author = { K.B. Johnsen and A. Burkhart and F. Melander and P.J. Kempen and J.B. Vejlebo and P. Siupka and M.S. Nielsen and T.L. Andresen and T. Moos},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85028842976&doi=10.1038%2fs41598-017-11220-1&partnerID=40&md5=4a74f8e523756c8e725e48221447c7a2},
doi = {10.1038/s41598-017-11220-1},
issn = {20452322},
year = {2017},
date = {2017-01-01},
journal = {Scientific Reports},
volume = {7},
number = {1},
publisher = {Nature Publishing Group},
abstract = {Drug delivery to the brain is hampered by the presence of the blood-brain barrier, which excludes most molecules from freely diffusing into the brain, and tightly regulates the active transport mechanisms that ensure sufficient delivery of nutrients to the brain parenchyma. Harnessing the possibility of delivering neuroactive drugs by way of receptors already present on the brain endothelium has been of interest for many years. The transferrin receptor is of special interest since its expression is limited to the endothelium of the brain as opposed to peripheral endothelium. Here, we investigate the possibility of delivering immunoliposomes and their encapsulated cargo to the brain via targeting of the transferrin receptor. We find that transferrin receptor-targeting increases the association between the immunoliposomes and primary endothelial cells in vitro, but that this does not correlate with increased cargo transcytosis. Furthermore, we show that the transferrin receptor-targeted immunoliposomes accumulate along the microvessels of the brains of rats, but find no evidence for transcytosis of the immunoliposome. Conversely, the increased accumulation correlated both with increased cargo uptake in the brain endothelium and subsequent cargo transport into the brain. These findings suggest that transferrin receptor-targeting is a relevant strategy of increasing drug exposure to the brain. © 2017 The Author(s).},
note = {114},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nielsen, S. S. E.; Siupka, P.; Georgian, A.; Preston, J. E.; Tóth, A. E.; Yusof, S. R.; Abbott, N. J.; Nielsen, M. S.
Improved method for the establishment of an in Vitro Blood-Brain barrier model based on porcine brain endothelial cells Journal Article
In: Journal of Visualized Experiments, vol. 2017, no. 127, 2017, ISSN: 1940087X, (17).
@article{2-s2.0-85031048678,
title = {Improved method for the establishment of an in Vitro Blood-Brain barrier model based on porcine brain endothelial cells},
author = { S.S.E. Nielsen and P. Siupka and A. Georgian and J.E. Preston and A.E. Tóth and S.R. Yusof and N.J. Abbott and M.S. Nielsen},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85031048678&doi=10.3791%2f56277&partnerID=40&md5=2c91af7ab5ec96036e6e5c1de056bbd7},
doi = {10.3791/56277},
issn = {1940087X},
year = {2017},
date = {2017-01-01},
journal = {Journal of Visualized Experiments},
volume = {2017},
number = {127},
publisher = {Journal of Visualized Experiments},
abstract = {The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) models based on pBECs in mono-culture (MC), MC with astrocyte-conditioned medium (ACM), and non-contact co-culture (NCC) with astrocytes of porcine or rat origin. pBECs were isolated and cultured from fragments of capillaries from the brain cortices of domestic pigs 5-6 months old. These fragments were purified by careful removal of meninges, isolation and homogenization of grey matter, filtration, enzymatic digestion, and centrifugation. To further eliminate contaminating cells, the capillary fragments were cultured with puromycin-containing medium. When 60-95% confluent, pBECs growing from the capillary fragments were passaged to permeable membrane filter inserts and established in the models. To increase barrier tightness and BBB characteristic phenotype of pBECs, the cells were treated with the following differentiation factors: membrane permeant 8-CPT-cAMP (here abbreviated cAMP), hydrocortisone, and a phosphodiesterase inhibitor, RO-20-1724 (RO). The procedure was carried out over a period of 9-11 days, and when establishing the NCC model, the astrocytes were cultured 2-8 weeks in advance. Adherence to the described procedures in the protocol has allowed the establishment of endothelial layers with highly restricted paracellular permeability, with the NCC model showing an average transendothelial electrical resistance (TEER) of 1249 ± 80 Ω cm2, and paracellular permeability (Papp) for Lucifer Yellow of 0.90 10-6 ± 0.13 10-6 cm sec-1 (mean ± SEM; n=55). Further evaluation of this pBEC phenotype showed good expression of the tight junctional proteins claudin 5, ZO-1, occludin and adherens junction protein p120 catenin. The model presented can be used for a range of studies of the BBB in health and disease and, with the highly restrictive paracellular permeability, this model is suitable for studies of transport and intracellular trafficking. © 2017 Journal of Visualized Experiments.},
note = {17},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Siupka, P.; Hersom, M. N. S.; Lykke-Hartmann, K.; Johnsen, K. B.; Thomsen, L. B.; Andresen, T. L.; Moos, T.; Abbott, N. J.; Brodin, B.; Nielsen, M. S.
Bidirectional apical–basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells Journal Article
In: Journal of Cerebral Blood Flow and Metabolism, vol. 37, no. 7, pp. 2598-2613, 2017, ISSN: 0271678X, (17).
@article{2-s2.0-85021059483,
title = {Bidirectional apical–basal traffic of the cation-independent mannose-6-phosphate receptor in brain endothelial cells},
author = { P. Siupka and M.N.S. Hersom and K. Lykke-Hartmann and K.B. Johnsen and L.B. Thomsen and T.L. Andresen and T. Moos and N.J. Abbott and B. Brodin and M.S. Nielsen},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021059483&doi=10.1177%2f0271678X17700665&partnerID=40&md5=03355135c08e801c9ee529cc2a4ed0f8},
doi = {10.1177/0271678X17700665},
issn = {0271678X},
year = {2017},
date = {2017-01-01},
journal = {Journal of Cerebral Blood Flow and Metabolism},
volume = {37},
number = {7},
pages = {2598-2613},
publisher = {SAGE Publications Ltd},
abstract = {Brain capillary endothelium mediates the exchange of nutrients between blood and brain parenchyma. This barrier function of the brain capillaries also limits passage of pharmaceuticals from blood to brain, which hinders treatment of several neurological disorders. Receptor-mediated transport has been suggested as a potential pharmaceutical delivery route across the brain endothelium, e.g. reports have shown that the transferrin receptor (TfR) facilitates transcytosis of TfR antibodies, but it is not known whether this recycling receptor itself traffics from apical to basal membrane in the process. Here, we elucidate the endosomal trafficking of the retrograde transported cation-independent mannose-6-phosphate receptor (MPR300) in primary cultures of brain endothelial cells (BECs) of porcine and bovine origin. Receptor expression and localisation of MPR300 in the endo-lysosomal system and trafficking of internalised receptor are analysed. We also demonstrate that MPR300 can undergo bidirectional apical–basal trafficking in primary BECs in co-culture with astrocytes. This is, to our knowledge, the first detailed study of retrograde transported receptor trafficking in BECs, and the study demonstrates that MPR300 can be transported from the luminal to abluminal membrane and reverse. Such trafficking of MPR300 suggests that retrograde transported receptors in general may provide a mechanism for transport of pharmaceuticals into the brain. © 2017, © The Author(s) 2017.},
note = {17},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Richner, M.; Jager, S. B.; Siupka, P.; Vaegter, C. B.
Hydraulic extrusion of the spinal cord and isolation of dorsal root ganglia in rodents Journal Article
In: Journal of Visualized Experiments, vol. 2017, no. 119, 2017, ISSN: 1940087X, (45).
@article{2-s2.0-85011628882,
title = {Hydraulic extrusion of the spinal cord and isolation of dorsal root ganglia in rodents},
author = { M. Richner and S.B. Jager and P. Siupka and C.B. Vaegter},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85011628882&doi=10.3791%2f55226&partnerID=40&md5=d7a0a1c2f5f67313b2dfe1fbbd1a3bc4},
doi = {10.3791/55226},
issn = {1940087X},
year = {2017},
date = {2017-01-01},
journal = {Journal of Visualized Experiments},
volume = {2017},
number = {119},
publisher = {Journal of Visualized Experiments},
abstract = {Traditionally, the spinal cord is isolated by laminectomy, i.e. by breaking open the spinal vertebrae one at a time. This is both time consuming and may result in damage to the spinal cord caused by the dissection process. Here, we show how the spinal cord can be extruded using hydraulic pressure. Handling time is significantly reduced to only a few minutes, likely decreasing protein damage. The low risk of damage to the spinal cord tissue improves subsequent immunohistochemical analysis. By performing hydraulic spinal cord extrusion instead of traditional laminectomy, the rodents can further be used for DRG isolation, thereby lowering the number of animals and allowing analysis across tissues from the same rodent. We demonstrate a consistent method to identify and isolate the DRGs according to their localization relative to the costae. It is, however, important to adjust this method to the particular animal used, as the number of spinal cord segments, both thoracic and lumbar, may vary according to animal type and strain. In addition, we illustrate further processing examples of the isolated tissues. © 2017 Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.},
note = {45},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2016
Burkhart, A.; Skjørringe, T.; Johnsen, K. B.; Siupka, P.; Thomsen, L. B.; Nielsen, M. S.; Thomsen, L. L.; Moos, T.
In: Molecular Neurobiology, vol. 53, no. 10, pp. 7237-7253, 2016, ISSN: 08937648, (57).
@article{2-s2.0-84994754057,
title = {Expression of Iron-Related Proteins at the Neurovascular Unit Supports Reduction and Reoxidation of Iron for Transport Through the Blood-Brain Barrier},
author = { A. Burkhart and T. Skjørringe and K.B. Johnsen and P. Siupka and L.B. Thomsen and M.S. Nielsen and L.L. Thomsen and T. Moos},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84994754057&doi=10.1007%2fs12035-015-9582-7&partnerID=40&md5=a1d00492ac896de8a6394df4194b1c23},
doi = {10.1007/s12035-015-9582-7},
issn = {08937648},
year = {2016},
date = {2016-01-01},
journal = {Molecular Neurobiology},
volume = {53},
number = {10},
pages = {7237-7253},
publisher = {Humana Press Inc.},
abstract = {The mechanisms for iron transport through the blood-brain barrier (BBB) remain a controversy. We analyzed for expression of mRNA and proteins involved in oxidation and transport of iron in isolated brain capillaries from dietary normal, iron-deficient, and iron-reverted rats. The expression was also investigated in isolated rat brain endothelial cells (RBECs) and in immortalized rat brain endothelial (RBE4) cells grown as monoculture or in hanging culture inserts with defined BBB properties. Transferrin receptor 1, ferrireductases Steap 2 and 3, divalent metal transporter 1 (DMT1), ferroportin, soluble and glycosylphosphatidylinositol (GPI)-anchored ceruloplasmin, and hephaestin were all expressed in brain capillaries in vivo and in isolated RBECs and RBE4 cells. Gene expression of DMT1, ferroportin, and soluble and GPI-anchored ceruloplasmin were significantly higher in isolated RBECs with induced BBB properties. Primary pericytes and astrocytes both expressed ceruloplasmin and hephaestin, and RBECs, pericytes, and astrocytes all exhibited ferrous oxidase activity. The coherent protein expression of these genes was demonstrated by immunocytochemistry. The data show that brain endothelial cells provide the machinery for receptor-mediated uptake of ferric iron-containing transferrin. Ferric iron can then undergo reduction to ferrous iron by ferrireductases inside endosomes followed by DMT1-mediated pumping into the cytosol and subsequently cellular export by ferroportin. The expression of soluble ceruloplasmin by brain endothelial cells, pericytes, and astrocytes that together form the neurovascular unit (NVU) provides the ferroxidase activity necessary to reoxidize ferrous iron once released inside the brain. © 2015, Springer Science+Business Media New York.},
note = {57},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Akhtar, H.; Hamming, O. J.; Jan, S. U.; Akhtar, S.; Terczyńska-Dyla, E.; Siupka, P.; Shafique, A.; Hartmann, R.; Sadia, H.
Unraveling the molecular mechanism governing the tissue specific expression of IFNλR1 Journal Article
In: Pakistan Journal of Pharmaceutical Sciences, vol. 29, no. 3, pp. 795-799, 2016, ISSN: 1011601X.
@article{2-s2.0-84979666781,
title = {Unraveling the molecular mechanism governing the tissue specific expression of IFNλR1},
author = { H. Akhtar and O.J. Hamming and S.U. Jan and S. Akhtar and E. Terczyńska-Dyla and P. Siupka and A. Shafique and R. Hartmann and H. Sadia},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979666781&partnerID=40&md5=7da56c28d587744ff596ab6cfd149aa4},
issn = {1011601X},
year = {2016},
date = {2016-01-01},
journal = {Pakistan Journal of Pharmaceutical Sciences},
volume = {29},
number = {3},
pages = {795-799},
publisher = {Pakistan Journal of Pharmaceutical Sciences},
abstract = {The functional receptor for type III interferons (IFNs) is a heterodimer of IFNLR1 and IL10R2. IFNLR1 is expressed in a highly tissue specific manner, with epithelial and liver tissue as the prime expressing tissues in humans. However, knowledge about the molecular pathways responsible for regulating the expression of IFNLR1 is yet unknown. In this study, various bioinformatics tools were used to predict the scores of signal peptides of IFNλR1 and IFNαR1, which was considered as an important difference in the expression of both receptors or participation in regulating the IFNLR1 gene. In silico study revealed that the signal peptide of IFNαR1 had more potential than the signal peptide of IFNλR1 but changing the signal peptide of wild type IFNλR1 with the signal peptide of IFNαR1 in wet lab had barely shown any differences. Selective expression of IFNλR1 was considered to be a plus point towards the targeted anti-viral activity of IFNλs but artificial control on its expression will surely make IFNλs a better drug with enhanced activity. The results of this study may help us in contributing some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities involved.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2015
Siupka, P.; Hamming, O. J.; Kang, L.; Gad, H. H.; Hartmann, R.
A conserved sugar bridge connected to the WSXWS motif has an important role for transport of IL-21R to the plasma membrane Journal Article
In: Genes and Immunity, vol. 16, no. 6, pp. 405-413, 2015, ISSN: 14664879, (15).
@article{2-s2.0-84941021863,
title = {A conserved sugar bridge connected to the WSXWS motif has an important role for transport of IL-21R to the plasma membrane},
author = { P. Siupka and O.J. Hamming and L. Kang and H.H. Gad and R. Hartmann},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84941021863&doi=10.1038%2fgene.2015.22&partnerID=40&md5=2f1047c0e20db7130dd8f1719782e987},
doi = {10.1038/gene.2015.22},
issn = {14664879},
year = {2015},
date = {2015-01-01},
journal = {Genes and Immunity},
volume = {16},
number = {6},
pages = {405-413},
publisher = {Nature Publishing Group},
abstract = {Interleukin-21 (IL-21) is a class I cytokine that belongs to the γ c -subfamily of cytokines and regulates immune responses. It signals through a heterodimeric receptor complex composed of the IL-21R1 and γ c -receptor chains. A characteristic feature of class I cytokine receptors is the presence of a consensus motif WSXWS (WS motif) in the membrane proximal fibronectin type III domain (FNIII) of these receptors. We recently described the structure of the IL-21R:IL-21 complex and showed that the first tryptophan of the WS motif of IL-21R is mannosylated and involved in formation of a sugar bridge that connects the two FNIII domains of the receptor. Furthermore, a mutation within the WS motif of IL-21R was recently shown to cause a novel kind of primary immunodeficiency syndrome (PID). Here, we report the structure of IL-21R alone, which shows that the sugar bridge forms independently of whether IL-21R binds IL-21 or not, and we furthermore investigate the role of this bridge in the export of IL-21R and γC to the plasma membrane. Thus, we provide a molecular explanation for how mutations in the WS motif may cause PIDs. © 2015 Macmillan Publishers Limited.},
note = {15},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Klinger, S. C.; Siupka, P.; Nielsen, M. S.
Retromer-mediated trafficking of transmembrane receptors and transporters Journal Article
In: Membranes, vol. 5, no. 3, pp. 288-306, 2015, ISSN: 20770375, (19).
@article{2-s2.0-84937401553,
title = {Retromer-mediated trafficking of transmembrane receptors and transporters},
author = { S.C. Klinger and P. Siupka and M.S. Nielsen},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84937401553&doi=10.3390%2fmembranes5030288&partnerID=40&md5=d5400af8789d05168858a029cfc08ae5},
doi = {10.3390/membranes5030288},
issn = {20770375},
year = {2015},
date = {2015-01-01},
journal = {Membranes},
volume = {5},
number = {3},
pages = {288-306},
publisher = {MDPI AG},
abstract = {Transport between the endoplasmatic reticulum, the Golgi-network, the endo-lysosomal system and the cell surface can be categorized as anterograde or retrograde, describing traffic that goes forward or backward, respectively. Traffic going from the plasma membrane to endosomes and lysosomes or the trans-Golgi network (TGN) constitutes the major retrograde transport routes. Several transmembrane proteins undergo retrograde transport as part of a recycling mechanism that contributes to reutilization and maintenance of a steady-state protein localization. In addition, some receptors are hijacked by exotoxins and used for entry and intracellular transport. The physiological relevance of retrograde transport cannot be overstated. Retrograde trafficking of the amyloid precursor protein determines the distribution between organelles, and hence the possibility of cleavage by γ-secretase. Right balancing of the pathways is critical for protection against Alzheimer’s disease. During embryonic development, retrograde transport of Wntless to the TGN is essential for the following release of Wnt from the plasma membrane. Furthermore, overexpression of Wntless has been linked to oncogenesis. Here, we review relevant aspects of the retrograde trafficking of mammalian transmembrane receptors and transporters, with focus on the retromer-mediated transport between endosomes and the TGN. © 2015 by the authors; licensee MDPI, Basel, Switzerland},
note = {19},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2014
Siupka, P.; Hamming, O. J.; Frétaud, M.; Luftalla, G.; Levraud, J. P.; Hartmann, R.
The crystal structure of zebrafish IL-22 reveals an evolutionary, conserved structure highly similar to that of human IL-22 Journal Article
In: Genes and Immunity, vol. 15, no. 5, pp. 293-302, 2014, ISSN: 14664879, (17).
@article{2-s2.0-84905026036,
title = {The crystal structure of zebrafish IL-22 reveals an evolutionary, conserved structure highly similar to that of human IL-22},
author = { P. Siupka and O.J. Hamming and M. Frétaud and G. Luftalla and J.P. Levraud and R. Hartmann},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905026036&doi=10.1038%2fgene.2014.18&partnerID=40&md5=6ee6e430841abde756e8d0f89c9102a6},
doi = {10.1038/gene.2014.18},
issn = {14664879},
year = {2014},
date = {2014-01-01},
journal = {Genes and Immunity},
volume = {15},
number = {5},
pages = {293-302},
publisher = {Nature Publishing Group},
abstract = {The class II cytokine family consists of small -helical signaling proteins including the interleukin-10 (IL-10)/IL-22 family, as well as interferons (IFNs). They regulate the innate immune response and in addition have an important role in protecting epithelial tissues. Teleost fish possess a class II cytokine system surprisingly similar to that of humans, and thus zebrafish offers an attractive model organism for investigating the role of class II cytokines in inflammation. However, the evolution of class II cytokines is critical to understand if we are to take full advantage of zebrafish as a model system. The small size and fast evolution of these cytokines obscure phylogenetic analyses based purely on sequences, but one can overcome this obstacle by using information contained within the structure of those molecules. Here we present the crystal structure of IL-22 from zebrafish (zIL-22) solved at 2.1 Å, which displays a typical class II cytokine architecture. We generated a structure-guided alignment of vertebrate class II cytokines and used it for phylogenetic analysis. Our analysis suggests that IL-22 and IL-26 arose early during the evolution of the IL-10-like cytokines. Thus, we propose an evolutionary scenario of class II cytokines in vertebrates, based on genomic and structural data. © 2014 Macmillan Publishers Limited All rights reserved.},
note = {17},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2013
Hamming, O. J.; Terczyńska-Dyla, E.; Vieyres, G.; Dijkman, R.; Jørgensen, S. E.; Akhtar, H.; Siupka, P.; Pietschmann, T.; Thiel, V.; Hartmann, R.
Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses Journal Article
In: EMBO Journal, vol. 32, no. 23, pp. 3055-3065, 2013, ISSN: 02614189, (151).
@article{2-s2.0-84888876575,
title = {Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses},
author = { O.J. Hamming and E. Terczyńska-Dyla and G. Vieyres and R. Dijkman and S.E. Jørgensen and H. Akhtar and P. Siupka and T. Pietschmann and V. Thiel and R. Hartmann},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84888876575&doi=10.1038%2femboj.2013.232&partnerID=40&md5=09d2021b1201506a1817463963f435b3},
doi = {10.1038/emboj.2013.232},
issn = {02614189},
year = {2013},
date = {2013-01-01},
journal = {EMBO Journal},
volume = {32},
number = {23},
pages = {3055-3065},
abstract = {The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection. © 2013 European Molecular Biology Organization.},
note = {151},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Guzik, U.; Hupert-Kocurek, K. T.; Siupka, P.; Wojcieszyńska, D.
In: Przemysl Chemiczny, vol. 92, no. 4, pp. 458-462, 2013, ISSN: 00332496.
@article{2-s2.0-84877246424,
title = {Cinnamic acid and its hydroxy derivatives. Synthesis and application [Kwas cynamonowy i jego hydroksypochodne. Synteza i praktyczne zastosowania]},
author = { U. Guzik and K.T. Hupert-Kocurek and P. Siupka and D. Wojcieszyńska},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84877246424&partnerID=40&md5=0b74e0b28297a7e939a1f5cef04d4779},
issn = {00332496},
year = {2013},
date = {2013-01-01},
journal = {Przemysl Chemiczny},
volume = {92},
number = {4},
pages = {458-462},
abstract = {A review, with 39 refs., of methods for chem. and biochem. synthesis of cinnamic, p-cumaric and 2,3-dihydroxycinnamic acids as well as their further enzymatic conversion to the org. intermediates.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2011
Wojcieszyńska, D.; Guzik, U.; Hupert-Kocurek, K. T.; Siupka, P.
In: Przemysl Chemiczny, vol. 90, no. 8, pp. 1515-1519, 2011, ISSN: 00332496, (1).
@article{2-s2.0-80052438366,
title = {Microbial degradation of chlorophenols, hazardous wastes of chemical industry [Mikrobiologiczny rozkład chlorofenoli, uciaz•liwych odpadów przemyłu chemicznege]},
author = { D. Wojcieszyńska and U. Guzik and K.T. Hupert-Kocurek and P. Siupka},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80052438366&partnerID=40&md5=cbe5c3b9fad5e79642baf6df3e961fb0},
issn = {00332496},
year = {2011},
date = {2011-01-01},
journal = {Przemysl Chemiczny},
volume = {90},
number = {8},
pages = {1515-1519},
abstract = {A review, with 56 refs., of metabolic path ways for biochem. degrdn. of persistant Cl-contg. phenols, esp. via resp. chlorocatechols.},
note = {1},
keywords = {},
pubstate = {published},
tppubtype = {article}
}