Hyperoxia-induced NAD(P)H oxidase activation and regulation by map kinases in human lung endothelial cells

Narasimham L. Parinandi, Michael A. Kleinberg, Peter V. Usatyuk, Rhett J. Cummings, Arjun Pennathur, Arturo J. Cardounel, Jay L. Zweier, Joe G.N. Garcia, Viswanathan Natarajan

Research output: Contribution to journalReview article

178 Scopus citations

Abstract

Hyperoxia increases reactive oxygen species (ROS) production in vascular endothelium; however, the mechanisms involved in ROS generation are not well characterized. We determined the role and regulation of NAD(P)H oxidase in hyperoxia-induced ROS formation in human pulmonary artery endothelial cells (HPAECs). Exposure of HPAECs to hyperoxia for 1, 3, and 12 h increased the generation of superoxide anion, which was blocked by diphenyleneiodonium but not by rotenone or oxypurinol. Furthermore, hyperoxia enhanced NADPH- and NADH-dependent and superoxide dismutase- or diphenyleneiodonium-inhibitable ROS production in HPAECs. Immunohistocytochemistry and Western blotting revealed the presence of gp91, p67 phox, p22 phox, and p47 phox subcomponents of NADPH oxidase in HPAECs. Transfection of HPAECs with p22 phox antisense plasmid inhibited hyperoxia-induced ROS production. Exposure of HPAECs to hyperoxia activated p38 MAPK and ERK, and inhibition of p38 MAPK and MEK1/2 attenuated the hyperoxia-induced ROS generation. These results suggest a role for MAPK in regulating hyperoxia-induced NAD(P)H oxidase activation in HPAECs.

Original languageEnglish (US)
Pages (from-to)L26-L38
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume284
Issue number1 28-1
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Lung vascular endothelial cells
  • Mitogen-activated protein kinases
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Parinandi, N. L., Kleinberg, M. A., Usatyuk, P. V., Cummings, R. J., Pennathur, A., Cardounel, A. J., Zweier, J. L., Garcia, J. G. N., & Natarajan, V. (2003). Hyperoxia-induced NAD(P)H oxidase activation and regulation by map kinases in human lung endothelial cells. American Journal of Physiology - Lung Cellular and Molecular Physiology, 284(1 28-1), L26-L38.