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Overexpression of cationic amino acid transporter-1 increases nitric oxide production in hypoxic human pulmonary microvascular endothelial cells.
Cui, Hongmei; Chen, Bernadette; Chicoine, Louis G; Nelin, Leif D.
Afiliación
  • Cui H; Pulmonary Hypertension Group, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, The Ohio State University, Columbus, OH, USA.
Clin Exp Pharmacol Physiol ; 38(12): 796-803, 2011 Dec.
Article en En | MEDLINE | ID: mdl-21923750
1. The endogenous production of and/or the bioavailability of nitric oxide (NO) is decreased in pulmonary hypertensive diseases. L-arginine (L-arg) is the substrate for NO synthase (NOS). L-arg is transported into cells via the cationic amino acid transporters (CAT), of which there are two isoforms in endothelial cells, CAT-1 and CAT-2. 2. To test the hypothesis that hypoxia will decrease CAT expression and L-arg uptake resulting in decreased NO production in human pulmonary microvascular endothelial cells (hPMVEC), cells were incubated in either normoxia (21% O(2), 5% CO(2), balance N(2)) or hypoxia (1% O(2), 5% CO(2), balance N(2)). 3. The hPMVEC incubated in hypoxia had 80% less NO production than cells incubated in normoxia (P < 0.01). The hPMVEC incubated in hypoxia had significantly lower CAT-2 mRNA levels than normoxic hPMVEC (P < 0.005), and the transport of L-arg was 40% lower in hypoxic than in normoxic hPMVEC (P < 0.01). In hypoxic cells, overexpression of CAT-1 resulted in significantly greater L-arg transport and NO production (P < 0.05). 4. These results demonstrate that in hPMVEC, hypoxia decreased CAT-2 expression, L-arg uptake and NO production. Furthermore, the hypoxia-induced decrease in NO production in hPMVEC can be attenuated by overexpressing CAT in these cells. We speculate that the CAT may represent a novel therapeutic target for treating pulmonary hypertensive disorders.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Endotelio Vascular / Transportador de Aminoácidos Catiónicos 1 / Pulmón / Óxido Nítrico Límite: Humans Idioma: En Revista: Clin Exp Pharmacol Physiol Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Endotelio Vascular / Transportador de Aminoácidos Catiónicos 1 / Pulmón / Óxido Nítrico Límite: Humans Idioma: En Revista: Clin Exp Pharmacol Physiol Año: 2011 Tipo del documento: Article País de afiliación: Estados Unidos