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Titolo:
Oxidative stress increases synthesis of big endothelin-1 by activation of the endothelin-1 promoter
Autore:
Kahler, J; Mendel, S; Weckmuller, J; Orzechowski, HD; Mittmann, C; Koster, R; Paul, M; Meinertz, T; Munzel, T;
Indirizzi:
Univ Hamburg Hosp, Dept Cardiol, D-20246 Hamburg, Germany Univ Hamburg Hosp Hamburg Germany D-20246 diol, D-20246 Hamburg, Germany Univ Hamburg Hosp, Dept Pharmacol, D-20246 Hamburg, Germany Univ Hamburg Hosp Hamburg Germany D-20246 acol, D-20246 Hamburg, Germany Free Univ Berlin, Univ Hosp Benjamin Franklin, Dept Clin Pharmacol, D-1000Berlin, Germany Free Univ Berlin Berlin Germany D-1000 Pharmacol, D-1000Berlin, Germany
Titolo Testata:
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
fascicolo: 8, volume: 32, anno: 2000,
pagine: 1429 - 1437
SICI:
0022-2828(200008)32:8<1429:OSISOB>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUPEROXIDE ANION PRODUCTION; NITRIC-OXIDE; FUNCTIONAL-ANALYSIS; KAPPA-B; CELLS; HYPERTENSION; EXPRESSION; RELEASE; GENE; ATHEROSCLEROSIS;
Keywords:
oxygen-derived radicals; endothelin-1; preproendothelin-1 mRNA; promoter;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Munzel, T Univ Hamburg Hosp, Dept Cardiol, Martinistr 52, D-20246 Hamburg,Germany Univ Hamburg Hosp Martinistr 52 Hamburg Germany D-20246 Germany
Citazione:
J. Kahler et al., "Oxidative stress increases synthesis of big endothelin-1 by activation of the endothelin-1 promoter", J MOL CEL C, 32(8), 2000, pp. 1429-1437

Abstract

Modulation of the biosynthesis of the vasoconstrictor peptide endothelin-1by oxygen-derived free radicals generated by xanthine oxidase or hydrogen peroxide was studied in cultured endothelial cells. Endothelin-1 metabolismwas investigated at the level of endothelin-1 promoter, preproendothelin-1mRNA and intracellular big endothelin-1. Endothelin-1 mRNA, as characterized by Northern blotting, was increased both time-and dose-dependently by xanthine oxidase to up to 500% above baseline. Analysis of endothelin-1 promoter activity using a construct containing 1329 bp of the endothelin-1 promoter revealed that promoter activity was increased up to eight-fold by incubation with xanthine oxidase. Specificity was ascertained by co-incubation with superoxide dismutase and catalase leading to inhibition of the effect of xanthine oxidase. A significant contribution of nitric oxide was ruled out, since NOS III-mRNA transcription remained unchanged and L-NAME did not significantly alter endothelin-l promoter activity. Synthesis of intracellular big endothelin-1 protein was increased dose-dependently by xanthine oxidase. Our results indicate that oxidative stress leads to increased endothelial synthesis of big endothelin-1, which is a previously unknown mechanism and may help to understand the detrimental association of increased oxidative stress and elevated endothelin-1 levels in pathophysiological conditionspromoting atherosclerosis. (C) 2000 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 10:42:24