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

Charles I. Jones, Zhaosheng Han, Tennille Presley, Saradhadevi Varadharaj, Jay L. Zweier, Govindasamy Ilangovan, B. Rita Alevriadou

Research output: Contribution to journalArticlepeer-review

Abstract

Cultured vascular endothelial cell (EC) exposure to steady laminar shear stress results in peroxynitrite (ONOO-) 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 (O 2.-) generation leading to ONOO- formation and suppression of respiration. Electron paramagnetic resonance oximetry was used to measure O2 consumption rates of bovine aortic ECs sheared (10 dyn/cm2, 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- 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.- 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% O 2. Hence, the hyperoxia of in vitro EC flow studies, via increased NO and mitochondrial O2.- production, leads to enhanced ONOO- formation intramitochondrially and suppression of respiration.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume295
Issue number1
DOIs
StatePublished - Jul 2008
Externally publishedYes

Keywords

  • Endothelium
  • Mitochondria
  • Reactive oxygen species
  • Shear stress

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

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