Equilibrative nucleoside transporter 1 expression is downregulated by hypoxia in human umbilical vein endothelium.
Circ Res
; 97(1): 16-24, 2005 Jul 08.
Article
em En
| MEDLINE
| ID: mdl-15933265
Reduced oxygen level (hypoxia) induces endothelial dysfunction and release of the endogenous nucleoside adenosine. Human umbilical vein endothelium (HUVEC) function in an environment with 3% to 5% O2 and exhibit efficient adenosine membrane transport via human equilibrative nucleoside transporters 1 (hENT1). We studied whether adenosine transport and hENT1 expression are altered by hypoxia in HUVEC. Hypoxia (0 to 24 hours, 2% and 1% O2) reduced maximal hENT1-adenosine transport velocity (V(max)) and maximal nitrobenzylthionosine (NBMPR, a high-affinity hENT1 protein ligand) binding, but increased extracellular adenosine concentration. Hypoxia also reduced hENT1 protein and mRNA levels, effects unaltered by N(omega)-nitro-l-arginine methyl ester (l-NAME, nitric oxide synthase [NOS] inhibitor) or PD-98059 (inhibitor of mitogen-activated protein kinase kinase 1 and 2 [MEK1/2]). Hypoxia reduced endothelial NOS (eNOS) activity and eNOS phosphorylation at Ser(1177), but increased eNOS protein level. Hypoxia increased (1 to 3 hours), but reduced (24 hours) p42/44(mapk) phosphorylation. Thus, hypoxia-increased extracellular adenosine may result from reduced hENT1-adenosine transport in HUVEC. Hypoxia effect seems not to involve NO, but p42/44(mapk) may be required for the relatively rapid effect (1 to 3 hours) of hypoxia. These results could be important in diseases where the fetus is exposed to intrauterine environments poor in oxygen, such as intrauterine growth restriction, or where adenosine transport is altered, such as gestational diabetes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hipóxia Celular
/
Regulação da Expressão Gênica
/
Transportador Equilibrativo 1 de Nucleosídeo
/
Células Endoteliais
Tipo de estudo:
Etiology_studies
Limite:
Humans
Idioma:
En
Revista:
Circ Res
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Estados Unidos