Hypoxia/reoxygenation stimulates intracellular calcium oscillations in human aortic endothelial cells

Article

关键词: FREE-RADICAL GENERATION;    CANINE CORONARY-ARTERIES;    DEPENDENT RELAXATIONS;    AGGREGATING PLATELETS;    REOXYGENATION INJURY;    REPERFUSION INJURY;    HYDROGEN-PEROXIDE;    MECHANISM;    IMPAIRMENT;    MEMBRANE;   

DOI  :  10.1161/01.CIR.102.20.2541

来源: SCIE

【 摘 要 】

Background-We have previously shown that hydrogen peroxide stimulates endothelial [Ca2+](i) oscillations. This study was performed to determine whether posthypoxic reoxygenation stimulates [Ca2+](i) oscillations in vascular endothelial cells. Methods and Results-Hypoxia (glucose-free 95% N-2/5% CO2 bicarbonate buffer for 60 minutes) stimulated an increase in [Ca2+](i) from 111.9+/-7.9 to 161.7+/-17.7 nmol/L (n=12, P<0.01) in indo 1-loaded human aortic endothelial cells. On reoxygenation (glucose-containing 95% air/5% CO2 bicarbonate buffer), 13 of 16 cells responded with repetitive [Ca2+](i) oscillations with an average amplitude of 570.6+/-59.3 nmol/L, occurring at a mean interval of 0.28+/-0.04/min and persisting for 60 minutes. [Ca2+](i) oscillations were still observed in 4 of 7 cells studied in Ca2+-free buffer but did not occur when the intracellular Ca2+ store was first depleted during hypoxia by either 1 mu mol/L thapsigargin or by 10 mmol/L caffeine (n=6 for each). Reoxygenation-induced [Ca2+](i) oscillations were abolished by 10 mu mol/L diphenyleneiodonium, an inhibitor of NAD(P)H oxidase (n=7), and by polyethylene glycol (PEG)-catalase (5000 U/mL, n=4) but were not prevented by inhibitors of xanthine oxidase (n=5), cyclooxygenase(n=4), nitric oxide synthase (n=5), the mitochondrial electron transport chain (n=4), or by PEG-superoxide dismutase (n=5). Conclusions-Posthypoxic reoxygenation stimulates repetitive [Ca2+](i) oscillations that are dependent on Ca2+ release from an intracellular pool and require extracellular Ca2+ to be maintained. These oscillations may be initiated by NAD(P)H oxidase-derived hydrogen peroxide and may play a role in signal transduction during ischemia/reperfusion in vivo.

【 授权许可】

Free