Propofol protects against nitrosative stress-induced apoptotic insults to cerebrovascular endothelial cells via an intrinsic mitochondrial mechanism

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22 引文 斯高帕斯(Scopus)

摘要

Background. Cerebrovascular endothelial cells (CECs), major component cells of the blood-brain barrier, can be injured by oxidative stress. Propofol can protect cells from oxidative injury. The aim of this study was to evaluate the effects of propofol on nitrosative stress-induced insults to CECs and its possible mechanisms. Methods. Primary CECs isolated from mouse cerebral capillaries were exposed to2 nitric oxide (NO) donors: sodium nitroprusside (SNP) or S-nitrosoglutathione (GSNO). Cellular NO levels, cell morphologies, and cell viabilities were analyzed. DNA fragmentation and apoptotic cells were quantified using flow cytometry. Proapoptotic Bcl2-antagonist-killer (Bak) and cytochrome c were immunodetected. Bak translocation was analyzed using confocal microscopy. Caspases-9 and -3 activities were measured fluorometrically. Permeability of the CEC monolayer was assayed by measuring the transendothelial electrical resistance. Results. Exposure of CECs to SNP increased cellular NO levels and simultaneously decreased cell viability (P <.01). Meanwhile, treatment of CECs with propofol at a therapeutic concentration (50 μM) decreased SNP-induced cell death (P <.01). SNP induced DNA fragmentation and cell apoptosis, but propofol decreased the cell injury (P <.01). Sequentially, propofol decreased SNP-enhanced Bak levels and translocation from the cytoplasm to mitochondria (P <.05). Exposure of CECs to propofol attenuated GSNO-induced cell death, apoptosis, and caspase-3 activation (P <.01). Additionally, propofol protected CECs against SNP-induced disruption of the CEC monolayer (P <.05). Consequently, SNP-enhanced cascade activation of caspases-9 and -3 was decreased by propofol (P <.01). Conclusion. This study suggested that propofol at a therapeutic concentration can protect against nitrosative stress-induced apoptosis of CECs due to downregulation of the intrinsic Bak-mitochondrioncytochrome c-caspase protease pathway.
原文英語
頁(從 - 到)58-68
頁數11
期刊Surgery (United States)
154
發行號1
DOIs
出版狀態已發佈 - 7月 2013

ASJC Scopus subject areas

  • 手術

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