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dc.contributor.authorZemskova, Marina
dc.contributor.authorKurdyukov, Sergey
dc.contributor.authorJames, Joel
dc.contributor.authorMcClain, Nolan
dc.contributor.authorRafikov, Ruslan
dc.contributor.authorRafikova, Olga
dc.date.accessioned2020-12-16T01:42:26Z
dc.date.available2020-12-16T01:42:26Z
dc.date.issued2020-04-09
dc.identifier.citationZemskova, M., Kurdyukov, S., James, J., McClain, N., Rafikov, R., & Rafikova, O. (2020). Sex-specific stress response and HMGB1 release in pulmonary endothelial cells. Plos one, 15(4), e0231267.en_US
dc.identifier.issn1932-6203
dc.identifier.pmid32271800
dc.identifier.doi10.1371/journal.pone.0231267
dc.identifier.urihttp://hdl.handle.net/10150/649315
dc.description.abstractWomen are known to be associated with a higher susceptibility to pulmonary arterial hypertension (PAH). In contrast, male PAH patients have a worse survival prognosis. In this study, we investigated whether the contribution of sex goes beyond the effects of sex hormones by comparing the ability of isolated male and female pulmonary endothelial cells to respire, proliferate and tolerate the stress. Mouse lung endothelial cells (MLEC) were isolated from the lungs of male and female 3-week old mice. Male MLEC showed an increased basal mitochondrial respiration rate, elevated maximal respiration, a significantly greater level of mitochondrial polarization, and a higher rate of proliferation. Exposure of cells to hypoxia (2% of O-2 for 24 hours) induced a strong apoptotic response in female but not male MLEC. In contrast, treatment with mitochondrial respiratory Complex III inhibitor Antimycin A (AA, 50 mu M) mediated severe necrosis specifically in male MLEC, while female cells again responded primarily by apoptosis. The same effect with female cells responding to the stress by apoptosis and male cells responding by necrosis was confirmed in starved pulmonary endothelial cells isolated from human donors. Elevated necrosis seen in male cells was associated with a significant release of damage-associated alarmin, HMGB1. No stimuli induced a significant elevation of HMGB1 secretion in females. We conclude that male cells appear to be protected against mild stress conditions, such as hypoxia, possibly due to increased mitochondrial respiration. In contrast, they are more sensitive to impaired mitochondrial function, to which they respond by necrotic death. Necrosis in male vascular cells releases a significant amount of HMGB1 that could contribute to the pro-inflammatory phenotype known to be associated with the male gender.en_US
dc.language.isoenen_US
dc.publisherPUBLIC LIBRARY SCIENCEen_US
dc.rights© 2020 Zemskova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleSex-specific stress response and HMGB1 release in pulmonary endothelial cellsen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Div Endocrinol, Dept Meden_US
dc.identifier.journalPLOS ONEen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitlePloS one
dc.source.volume15
dc.source.issue4
dc.source.beginpagee0231267
dc.source.endpage
refterms.dateFOA2020-12-16T01:42:46Z
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States


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© 2020 Zemskova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.
Except where otherwise noted, this item's license is described as © 2020 Zemskova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.