Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Acta Physiol (Oxf) ; 200(1): 75-85, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20236253

RESUMO

AIM: The protein kinase B (PKB)/Akt is known to stimulate the cellular uptake of glucose and amino acids. The kinase is expressed in proximal renal tubules. The present study explored the influence of Akt/PKB on renal tubular phosphate transport. METHODS: The renal phosphate transporter NaPi-IIa was expressed in Xenopus oocytes with or without PKB/Akt and Na(+) phosphate cotransport determined using dual electrode voltage clamp. Renal phosphate excretion was determined in Akt2/PKBbeta knockout mice (akt2(-/-)) and corresponding wild-type mice (akt2(+/+)). Transporter protein abundance was determined using Western blotting and phosphate transport by (32)P uptake into brush border membrane vesicles. RESULTS: The phosphate-induced current in NaPi-IIa-expressing Xenopus oocytes was significantly increased by the coexpression of Akt/PKB. Phosphate excretion [micromol per 24 h per g BW] was higher by 91% in akt2(-/-) than in akt2(+/+) mice. The phosphaturia of akt2(-/-) mice occurred despite normal transport activity and expression of the renal phosphate transporters NaPi-IIa, NaPi-IIc and Pit2 in the brush border membrane, a significantly decreased plasma PTH concentration (by 46%) and a significantly enhanced plasma 1,25-dihydroxyvitamin D(3) concentration (by 46%). Moreover, fractional renal Ca(2+) excretion was significantly enhanced (by 53%) and bone density significantly reduced (by 11%) in akt2(-/-) mice. CONCLUSIONS: Akt2/PKBbeta plays a role in the acute regulation of renal phosphate transport and thus contributes to the maintenance of phosphate balance and adequate mineralization of bone.


Assuntos
Túbulos Renais/enzimologia , Fosfatos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/metabolismo , Animais , Transporte Biológico , Biomarcadores/sangue , Biomarcadores/urina , Western Blotting , Calcificação Fisiológica , Calcitriol/sangue , Feminino , Homeostase , Hipofosfatemia Familiar/enzimologia , Hipofosfatemia Familiar/genética , Masculino , Potenciais da Membrana , Camundongos , Camundongos Knockout , Microvilosidades/enzimologia , Hormônio Paratireóideo/sangue , Técnicas de Patch-Clamp , Proteínas Proto-Oncogênicas c-akt/deficiência , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Sódio/metabolismo , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/genética , Xenopus
2.
Cell Death Differ ; 12(5): 415-28, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15746942

RESUMO

Hyperosmotic shock, energy depletion, or removal of extracellular Cl(-) activates Ca(2+)-permeable cation channels in erythrocyte membranes. Subsequent Ca(2+) entry induces erythrocyte shrinkage and exposure of phosphatidylserine (PS) at the erythrocyte surface. PS-exposing cells are engulfed by macrophages. The present study explored the signalling involved. Hyperosmotic shock and Cl(-) removal triggered the release of prostaglandin E(2) (PGE(2)). In whole-cell recording, activation of the cation channels by Cl(-) removal was abolished by the cyclooxygenase inhibitor diclophenac. In FACS analysis, phospholipase-A(2) inhibitors quinacrine and palmitoyltrifluoromethyl-ketone, and cyclooxygenase inhibitors acetylsalicylic acid and diclophenac, blunted the increase of PS exposure following Cl(-) removal. PGE(2) (but not thromboxane) induced cation channel activation, increase in cytosolic Ca(2+) concentration, cell shrinkage, PS exposure, calpain activation, and ankyrin-R degradation. The latter was attenuated by calpain inhibitors-I/II, while PGE(2)-induced PS exposure was not. In conclusion, hyperosmotic shock or Cl(-) removal stimulates erythrocyte PS exposure through PGE(2) formation and subsequent activation of Ca(2+)-permeable cation channels.


Assuntos
Apoptose/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Prostaglandinas E/metabolismo , Anquirinas/metabolismo , Anexinas/metabolismo , Cálcio/metabolismo , Canais de Cálcio/efeitos dos fármacos , Calpaína/metabolismo , Tamanho Celular/efeitos dos fármacos , Cloretos/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Citosol/efeitos dos fármacos , Diclofenaco/farmacologia , Inibidores Enzimáticos/farmacologia , Citometria de Fluxo , Humanos , Modelos Biológicos , Pressão Osmótica/efeitos dos fármacos , Técnicas de Patch-Clamp , Fosfatidilserinas/metabolismo , Fosfolipases A/metabolismo , Prostaglandinas E/farmacologia , Quinacrina/farmacologia , Solução Salina Hipertônica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...