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dc.rights.licenseCC BY — Creative Commons Attribution
dc.contributor.authorKo, Kenta
dc.contributor.authorSuzuki, Takehiro
dc.contributor.authorIshikawa, Ryota
dc.contributor.authorHattori, Natsuko
dc.contributor.authorIto, Risako
dc.contributor.authorUmehara, Kenta
dc.contributor.authorFurihata, Tomomi
dc.contributor.authorDohmae, Naoshi
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorIgarashi, Kazuei
dc.contributor.authorToida, Toshihiko
dc.contributor.authorHigashi, Kyohei
dc.date2020
dc.date.accessioned2022-06-21T14:01:00Z
dc.date.available2022-06-21T14:01:00Z
dc.date.issued2020-12-25
dc.identifier.citationIschemic stroke disrupts the endothelial glycocalyx through activation of proHPSE via acrolein exposure, K. Ko, T. Suzuki, R. Ishikawa, N. Hattori, K. Umehara, R. Ito, T. Furihata, N. Dohmae, R. J. Linhardt, K. Igarashi, T. Toida, K. Higashi, Journal of Biological Chemistry, 295, 18614-18624, 2020.
dc.identifier.issn1083351X
dc.identifier.issn219258
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5045
dc.identifier.urihttps://doi.org/10.1074/jbc.RA120.015105
dc.descriptionJournal of Biological Chemistry, 295, 18614-18624
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractInfiltration of peripheral immune cells after blood-brain barrier dysfunction causes severe inflammation after a stroke. Although the endothelial glycocalyx, a network of membrane-bound glycoproteins and proteoglycans that covers the lumen of endothelial cells, functions as a barrier to circulating cells, the relationship between stroke severity and glycocalyx dysfunction remains unclear. In this study, glycosaminoglycans, a component of the endothelial glycocalyx, were studied in the context of ischemic stroke using a photochemically induced thrombosis mouse model. Decreased levels of heparan sulfate and chondroitin sulfate and increased activity of hyaluronidase 1 and heparanase (HPSE) were observed in ischemic brain tissues. HPSE expression in cerebral vessels increased after stroke onset and infarct volume greatly decreased after co-administration of N-acetylcysteine + glycosaminoglycan oligosaccharides as compared with N-acetylcysteine administration alone. These results suggest that the endothelial glycocalyx was injured after the onset of stroke. Interestingly, scission activity of proHPSE produced by immortalized endothelial cells and HEK293 cells transfected with hHPSE1 cDNA were activated by acrolein (ACR) exposure. We identified the ACR-modified amino acid residues of proHPSE using nano LC–MS/MS, suggesting that ACR modification of Lys139 (6-kDa linker), Lys107, and Lys161, located in the immediate vicinity of the 6-kDa linker, at least in part is attributed to the activation of proHPSE. Because proHPSE, but not HPSE, localizes outside cells by binding with heparan sulfate proteoglycans, ACR-modified proHPSE represents a promising target to protect the endothelial glycocalyx.
dc.description.sponsorshipOffice of Disease Prevention and Health Promotion
dc.languageen_US
dc.language.isoENG
dc.publisherThe American Society for Biochemistry and Molecular Biology (ASBMB) and Elsevier
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofJournal of Biological Chemistry
dc.relation.urihttps://harc.rpi.edu/
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleIschemic stroke disrupts the endothelial glycocalyx through activation of proHPSE via acrolein exposureen_US
dc.typeArticle
dcterms.accessRightsA full text version is available in DSpace@RPI
dcterms.accessRightsOpen Access
dcterms.isPartOfJournal
dcterms.isVersionOfhttps://doi.org/10.1074/jbc.RA120.015105
dc.rights.holderCC BY : this license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. Credit must be given to the authors and the original work must be properly cited.
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
rpi.description.pages18614-18624
rpi.description.volume295


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Except where otherwise noted, this item's license is described as CC BY — Creative Commons Attribution