In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 291, No. 2 ( 2006-08), p. C357-C365
Abstract:
Particulate matter (PM) induces oxidative stress and cardiovascular adverse health effects, but the mechanistic link between the two is unclear. We hypothesized that PM enhanced oxidative stress in vascular endothelial cells and investigated the enzymatic sources of reactive oxygen species and their effects on mitogen-activated protein kinase (MAPK) activation and vasoconstriction. We measured the production of extracellular H 2 O 2 , activation of extracellular signal-regulated kinases1/2 (ERK1/2) and p38 MAPKs in human pulmonary artery endothelial cells (HPAEC) treated with urban particles (UP; SRM1648), and assessed the effects of H 2 O 2 on vasoconstriction in pulmonary artery ring and isolated perfused lung. Within minutes after UP treatment, HPAEC increased H 2 O 2 production that could be inhibited by diphenyleneiodonium (DPI), apocynin (APO), and sodium azide (NaN 3 ). The water-soluble fraction of UP as well as its two transition metal components, Cu and V, also stimulated H 2 O 2 production. NaN 3 inhibited H 2 O 2 production stimulated by Cu and V, whereas DPI and APO inhibited only Cu-stimulated H 2 O 2 production. Inhibitors of other H 2 O 2 -producing enzymes, including N ω -methyl-l-argnine, indomethacin, allopurinol, cimetidine, rotenone, and antimycin, had no effects. DPI but not NaN 3 attenuated UP-induced pulmonary vasoconstriction and phosphorylation of ERK1/2 and p38 MAPKs. Knockdown of p47phox gene expression by small interfering RNA attenuated UP-induced H 2 O 2 production and phosphorylation of ERK1/2 and p38 MAPKs. Intravascular administration of H 2 O 2 generated by glucose oxidase increased pulmonary artery pressure. We conclude that UP induce oxidative stress in vascular endothelial cells by activating NAD(P)H oxidase and the mitochondria. The endothelial oxidative stress may be an important mechanism for PM-induced acute cardiovascular health effects.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00365.2005
Language:
English
Publisher:
American Physiological Society
Publication Date:
2006
detail.hit.zdb_id:
1477334-X
SSG:
12
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