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

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...

Full description

Saved in:
Bibliographic Details
Published inAmerican journal of physiology. Lung cellular and molecular physiology Vol. 28; no. 1; pp. L26 - L38
Main Authors PARINANDI, Narasimham L, KLEINBERG, Michael A, USATYUK, Peter V, CUMMINGS, Rhett J, PENNATHUR, Arjun, CARDOUNEL, Arturo J, ZWEIER, Jay L, GARCIA, Joe G. N, NATARAJAN, Viswanathan
Format Journal Article
LanguageEnglish
Published Bethesda, MD American Physiological Society 2003
Subjects
Biological and medical sciences
Cells
Chemical and industrial products toxicology. Toxic occupational diseases
Gas, fumes
Lungs
Medical sciences
Neurotransmitters
Toxicology
Human
Cell culture
Endothelial cell
Oxygen
Enzyme
Toxicity
lung vascular endothelial cells
Lung
Oxidase
Mitogen-activated protein kinase
Environmental factor
Activation
Respiratory system
In vitro
Pulmonary artery
Free radical
Regulation(control)
NADH
Blood vessel
Hyperoxia
mitogen-activated protein kinases
reactive oxygen species
Circulatory system
Oxidoreductases
Online AccessGet full text

Cover

More Information
Summary: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.
ISSN:1040-0605
1522-1504