Hypoxia–reoxygenation-induced mitochondrial damage and apoptosis in human endothelial cells are inhibited by vitamin C

Dhar-Mascareño, Manya; Cárcamo, Juan M.; Golde, David W.

doi:10.1016/j.freeradbiomed.2005.01.017

Cited by 130 publications

(77 citation statements)

References 75 publications

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“…These studies showed that the mitochondria are a source of EC ROS production following H or anoxia (1-2 h)/RO (1 h), the ROS release site is the ETC complex III, and the neutrophil-EC adhesion at prolonged RO (10 h) is mediated by the postanoxic EC mitochondrial ROS production (32,33,71). RO following H (4 h) induced loss of mitochondrial membrane potential and cytochrome c release, suggesting the mitochondria as the initiation site of EC apoptosis (20). However, H/RO studies do not include the flow component that is essential in the RP phase of I/RP, and, as a result, do not provide information on the shear-induced NO generation upon RP and the resultant mitochondrial ROS/RNS production.…”

Section: Discussionmentioning

confidence: 99%

Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite

Jones¹,

Han²,

Presley³

et al. 2008

American Journal of Physiology-Cell Physiology

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Cultured vascular endothelial cell (EC) exposure to steady laminar shear stress results in peroxynitrite (ONOO Ϫ ) formation intramitochondrially and inactivation of the electron transport chain. We examined whether the "hyperoxic state" of 21% O2, compared with more physiological O2 tensions (PO2), increases the shear-induced nitric oxide (NO) synthesis and mitochondrial superoxide (O2 ⅐ Ϫ ) generation leading to ONOO Ϫ formation and suppression of respiration. Electron paramagnetic resonance oximetry was used to measure O2 consumption rates of bovine aortic ECs sheared (10 dyn/cm 2 , 30 min) at 5%, 10%, or 21% O2 or left static at 5% or 21% O2. Respiration was inhibited to a greater extent when ECs were sheared at 21% O2 than at lower PO2 or left static at different PO2. Flow in the presence of an endothelial NO synthase (eNOS) inhibitor or a ONOO Ϫ scavenger abolished the inhibitory effect. EC transfection with an adenovirus that expresses manganese superoxide dismutase in mitochondria, and not a control virus, blocked the inhibitory effect. Intracellular and mitochondrial O2 ⅐ Ϫ production was higher in ECs sheared at 21% than at 5% O2, as determined by dihydroethidium and MitoSOX red fluorescence, respectively, and the latter was, at least in part, NO-dependent. Accumulation of NO metabolites in media of ECs sheared at 21% O2 was modestly increased compared with ECs sheared at lower PO2, suggesting that eNOS activity may be higher at 21% O2. Hence, the hyperoxia of in vitro EC flow studies, via increased NO and mitochondrial O2 ⅐ Ϫ production, leads to enhanced ONOO Ϫ formation intramitochondrially and suppression of respiration. shear stress; endothelium; mitochondria; reactive oxygen species MITOCHONDRIA ARE THE SUBCELLULAR organelles for the production of cellular energy, but they also activate intracellular signaling pathways that modulate cell proliferation or promote cell cycle arrest and apoptosis by oxidative or nitrosative reactions. These reactions are regulated by the matrix concentration of nitric oxide (NO), which diffuses to the mitochondria from the cytosolic NO synthase (NOS) isoforms and is thought to be produced also locally by a mitochondrial NOS variant (11). In rat heart, skeletal muscle and liver mitochondria (15,57,58), isolated rat hearts (59), and whole animals (68), NO at physiological concentrations binds reversibly and in competition with oxygen (O 2 ) to the reduced binuclear center Cu B /a 3 of cytochrome-c oxidase (complex IV) of the electron transport chain (ETC) and inhibits mitochondrial O 2 uptake. At slightly higher concentrations, NO oxidizes ubiquinol of ubiquinolcytochrome c reductase (complex III) to increase unstable ubisemiquinone, which, by univalent electron transfer to O 2 , produces the reactive O 2 species (ROS) superoxide (O 2 ⅐ Ϫ ) (57, 58). O 2 ⅐ Ϫ generated from that location is released both into the matrix and intermembrane space (51), where it is dismutated to hydrogen peroxide (H 2 O 2 ) by manganese superoxide dismutase (MnSOD) and copper zinc SOD (CuZ...

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Section: Discussionmentioning

confidence: 99%

Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite

Jones¹,

Han²,

Presley³

et al. 2008

American Journal of Physiology-Cell Physiology

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“…Different types of chaperones involved in transporting substances across membranes, such as mitochondria and endoplasmic reticulum, are involved in correcting the potential harm that results from improper protein folding 3 . In recent data on the role of HSP70 to stabilize the hypoxia-inducible factor (HIF-1a), which in conditions of ischemia are responsible for the expression of erythropoietin gene and another approximately 60 genes whose products are involved in processes such as cell proliferation, apoptosis, angiogenesis, stabilization of protein molecules under conditions of oxidative stress [14][15][16][17] . Under hypoxic conditions, at least one of the chaperones (HSP70) is displaced from the complex with HIF-1a protein ARNT, which for 20-30 min hypoxia protects the structure factor of the impact of proteolysis.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Modulation of Heat Shock Protein 70 (HSP70)—Dependent Mechanisms of Endogenous Neuroprotection in Conditions of Prenatal Chronic Alcoholism by Cerebrocurin and Tiocetam

Бєленічев

Sokolik

Bukhtiarova

et al. 2016

Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychophar

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Objective:One of the primary reactions of the genome in response to stress is different genesis induction of heat shock proteins -HSP. The purpose of this study was to investigate the concentration of heat shock protein (HSP70) and hypoxia-inducible factor (HIF-1) in the brain of rats undergoing chronic prenatal alcoholism in different periods of ischemia and define the role of these proteins in the implementation of neuroprotective effect of Cerebrocurin and Tiocetam.

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“…Our population cell levels were linked to sleep apneahypopnea syndrome severity: greater severity correlated with lower levels of these cells. Hypoxia/re-oxygenation induces damage and apoptosis in human cells, 20 and continuous cycles of hypoxia/re-oxygenation can increase the production of oxidants. 18 We found that markers of protection against oxidation correlated positively with the levels of CD45Ϫ, CD34ϩ, KDRϩ, and CD133ϩ cells, whereas the levels of superoxide anion correlated negatively.…”

Section: Discussionmentioning

confidence: 99%

Effect of CPAP on Oxidative Stress and Circulating Progenitor Cell Levels in Sleep Patients With Apnea-Hypopnea Syndrome

Murri

García-Delgado²,

Alcázar-Ramírez³

et al. 2011

Respir Care

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BACKGROUND:The sleep apnea-hypopnea syndrome is associated with elevated oxidative stress, which is associated with reduced levels and functional impairment of progenitor cells. OBJEC-TIVE: To evaluate whether one month of CPAP treatment affects circulating-progenitor-cell levels and oxidative stress in patients with sleep apnea-hypopnea syndrome. METHODS: We enrolled 13 patients with sleep apnea-hypopnea syndrome who required nasal CPAP. We evaluated whiteblood-cell oxidative stress and CD45؊, CD34؉, KDR؉, and CD133؉ cell levels via flow-cytometry, before and one month after CPAP treatment. RESULTS: Superoxide anion and hydrogen peroxide were reduced, and markers of protection against oxidative stress were increased after CPAP. Progenitor-cell levels increased significantly after CPAP. There was a significant negative correlation between CD45؊, CD34؉, KDR؉, and CD133؉ cell levels and the severity of sleep apneahypopnea syndrome and superoxide anion. CONCLUSIONS: CD45؊, CD34؉, KDR؉, and CD133؉ cell levels rose significantly and reached values close to those in the control group after one month of CPAP. This change was accompanied by a significant decrease in oxidative stress, and no change in anthropometric or metabolic variables, including insulin resistance, weight, blood pressure, or lipid levels; consequently, the increase in progenitor-cell levels might be attributable to reduced oxidative stress.

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Hypoxia–reoxygenation-induced mitochondrial damage and apoptosis in human endothelial cells are inhibited by vitamin C

Cited by 130 publications

References 75 publications

Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite

Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite

Pharmacological Modulation of Heat Shock Protein 70 (HSP70)—Dependent Mechanisms of Endogenous Neuroprotection in Conditions of Prenatal Chronic Alcoholism by Cerebrocurin and Tiocetam

Effect of CPAP on Oxidative Stress and Circulating Progenitor Cell Levels in Sleep Patients With Apnea-Hypopnea Syndrome

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