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

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Abstract

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.

Original languageEnglish
Pages (from-to)58-68
Number of pages11
JournalSurgery
Volume154
Issue number1
DOIs
Publication statusPublished - Jul 2013

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Propofol
Endothelial Cells
Nitroprusside
Caspase 3
Caspase 9
DNA Fragmentation
Apoptosis
Cell Survival
Nitric Oxide
Cell Death
S-Nitrosoglutathione
Nitric Oxide Donors
Wounds and Injuries
Cellular Structures
Caspases
Cytochromes c
Blood-Brain Barrier
Electric Impedance
Confocal Microscopy
Permeability

ASJC Scopus subject areas

  • Surgery
  • Medicine(all)

Cite this

@article{639b9b5abcbc45f688cc7f1eb31aa8f8,
title = "Propofol protects against nitrosative stress-induced apoptotic insults to cerebrovascular endothelial cells via an intrinsic mitochondrial mechanism",
abstract = "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.",
author = "Ruei-Ming Chen and Yu-Ting Tai and Tyng-Guey Chen and Lin, {The Hin} and Chang, {Huai Chia} and Ta-Liang Chen and Gong-Jhe Wu",
year = "2013",
month = "7",
doi = "10.1016/j.surg.2013.02.003",
language = "English",
volume = "154",
pages = "58--68",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "1",

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TY - JOUR

T1 - Propofol protects against nitrosative stress-induced apoptotic insults to cerebrovascular endothelial cells via an intrinsic mitochondrial mechanism

AU - Chen, Ruei-Ming

AU - Tai, Yu-Ting

AU - Chen, Tyng-Guey

AU - Lin, The Hin

AU - Chang, Huai Chia

AU - Chen, Ta-Liang

AU - Wu, Gong-Jhe

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

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U2 - 10.1016/j.surg.2013.02.003

DO - 10.1016/j.surg.2013.02.003

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AN - SCOPUS:84883594005

VL - 154

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JO - Surgery

JF - Surgery

SN - 0039-6060

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