Upregulation of endothelial and inducible nitric oxide synthase expression by reactive oxygen species.
Am J Hypertens
; 21(1): 28-34, 2008 Jan.
Article
em En
| MEDLINE
| ID: mdl-18091741
ABSTRACT
BACKGROUND:
The effect of reactive oxygen species (ROS) on nitric oxide synthase (NOS) expression remains uncertain. This study explored the effect of increased ROS activity on NOS expression in vitro in human coronary artery endothelial cells (HCAECs) grown in culture and in intact animals.METHODS:
Endothelial NOS (eNOS) expression and nuclear factor kappaB (NFkappaB) activation were determined in HCAECs grown in culture and exposed to oxidative stress with xanthine-xanthine oxidase (X-XO) generated superoxide, H(2)O(2), or glutathione depletion with buthionine sulfoximine (BSO) for 24 h. In parallel experiments, cells were treated with a nitric oxide (NO) scavenger (hemoglobin), and with an NO donor S-nitroso-N-acetyl penicillamine (SNAP)]. In addition, eNOS and inducible NOS (iNOS) expressions were determined in rats treated with either BSO or vehicle for 48 h.RESULTS:
Increases in ROS activity, achieved by exogenous superoxide and H(2)O(2) or by glutathione depletion, upregulated the expression of eNOS at both transcriptional and translational levels in HCAECs. Similar effects were seen with the non-radical NO scavenger, hemoglobin. The upregulatory action of hemoglobin on eNOS messenger RNA (mRNA) and protein expressions was overcome by the NO donor, SNAP, thereby suggesting that there is a negative feedback regulation of eNOS by NO. Nuclear translocation of NFkappaB (p65) was noted within 5 min of exposure to H(2)O(2) and at least 15 min after exposure to superoxide or BSO. Induction of oxidative stress by glutathione depletion led to upregulation of renal and aorta eNOS and iNOS in live animals.CONCLUSIONS:
An increase in ROS activity upregulates NOS expression in vitro in HCAECs grown in culture, and also in vivo in animals. This effect appears to be, in part, mediated by limiting the availability of NO, thereby exerting a negative feedback influence on NOS expression through activation of NFkappaB.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação Enzimológica da Expressão Gênica
/
Espécies Reativas de Oxigênio
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Estresse Oxidativo
/
Células Endoteliais
/
Óxido Nítrico Sintase Tipo II
/
Óxido Nítrico Sintase Tipo III
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Am J Hypertens
Assunto da revista:
ANGIOLOGIA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos