Quantitative Proteomics Reveals the Beneficial Effects of Low Glucose on Neuronal Cell Survival in an in vitro Ischemic Penumbral Model

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dc.contributor.authorLi, Huaen
dc.contributor.authorKittur, Farooqahmed S.en
dc.contributor.authorHung, Chiu-Yuehen
dc.contributor.authorLi, P. Andyen
dc.contributor.authorGe, Xinghongen
dc.contributor.authorSane, David C.en
dc.contributor.authorXie, Jiahuaen
dc.contributor.departmentVirginia Tech Carilion School of Medicineen
dc.date.accessioned2021-02-09T14:10:49Zen
dc.date.available2021-02-09T14:10:49Zen
dc.date.issued2020-09-01en
dc.description.abstractUnderstanding proteomic changes in the ischemic penumbra are crucial to rescue those salvageable cells and reduce the damage of an ischemic stroke. Since the penumbra region is dynamic with heterogeneous cells/tissues, tissue sampling from animal models of stroke for the molecular study is a challenge. In this study, cultured hippocampal HT22 cells under hypoxia treatment for 17.5 h with 0.69 mM low glucose (H+LG) could mimic ischemic penumbral cells since they had much higher cell viability and viable cell number compared to hypoxia without glucose (H-G) treatment. To validate established cell-based ischemic penumbral model and understand the beneficial effects of low glucose (LG), quantitative proteomics analysis was performed on H+LG, H-G, and normoxia with normal 22 mM glucose (N+G) treated cells. We identified 427 differentially abundant proteins (DAPs) between H-G and N+G and further identified 105 DAPs between H+LG and H-G. Analysis of 105 DAPs revealed that LG promotes cell survival by activating HIF1 alpha to enhance glycolysis; preventing the dysregulations of extracellular matrix remodeling, cell cycle and division, and antioxidant and detoxification; as well as attenuating inflammatory reaction response, protein synthesis and neurotransmission activity. Our results demonstrated that this established cell-based system could mimic penumbral conditions and can be used for molecular studies.en
dc.description.notesThis work was supported by grants from the National Institute of General Medical Sciences (SC1GM111178-01A1) to JX.en
dc.description.sponsorshipNational Institute of General Medical SciencesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [SC1GM111178-01A1]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fncel.2020.00272en
dc.identifier.eissn1662-5102en
dc.identifier.other272en
dc.identifier.pmid33033473en
dc.identifier.urihttp://hdl.handle.net/10919/102316en
dc.identifier.volume14en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectneuronal cellsen
dc.subjectischemic penumbraen
dc.subjecthypoxiaen
dc.subjectlow glucoseen
dc.subjectproteomic analysisen
dc.titleQuantitative Proteomics Reveals the Beneficial Effects of Low Glucose on Neuronal Cell Survival in an in vitro Ischemic Penumbral Modelen
dc.title.serialFrontiers in Cellular Neuroscienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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