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Cell Calcium ; 39(5): 401-15, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16529812

RESUMO

The mammalian homologues of the Drosophila transient receptor potential (TRP) represent a superfamily of ion channels involved in Ca(2+) homeostasis. Several members of this family are activated either by a depletion of the internal stores of Ca(2+) or by stimulation of G protein-coupled receptors. In androgen responsive prostate cancer cell line LNCaP, TRPC1, TRPC4 and/or TRPV6 have been reported to function as store-operated channels (SOCs) while TRPC3 might be involved in the response to agonist stimulation, possibly through the induction of diacylglycerol production by phospholipase C. However, the control of expression of these TRP proteins is largely unknown. In the present study, we have investigated if the expression of the TRP proteins possibly involved in the capacitative influx of calcium is influenced by the contents of Ca(2+) in the endoplasmic reticulum. Using real-time PCR and Western blot techniques, we show that the expression of TRPC1, TRPC3 and TRPV6 proteins increases after a prolonged (24-48 h) depletion of the stores with thapsigargin. The upregulation of TRPC1 and TRPC3 depends on the store contents level and involves the activation of the Ca(2+)/calmodulin/calcineurin/NFAT pathway. Functionally, cells overexpressing TRPC1, TRPC3 and TRPV6 channels after a prolonged depletion of the stores showed an increased [Ca(2+)](i) response to alpha-adrenergic stimulation. However, the store-operated entry of calcium was unchanged. The isolated overexpression of TRPV6 (without overexpression of TRPC1 and TRPC3) did not produce this increased response to agonists, therefore suggesting that TRPC1 and/or TRPC3 proteins are responsible for the response to alpha-adrenergic stimulation but that TRPC1, TPRC3 and TRPV6 proteins, expressed alone or concomitantly, are not sufficient for SOC formation.


Assuntos
Sinalização do Cálcio , Cálcio/fisiologia , Canais de Cátion TRPC/genética , Canais de Cátion TRPV/genética , Agonistas alfa-Adrenérgicos/metabolismo , Agonistas alfa-Adrenérgicos/farmacologia , Western Blotting , Calcineurina/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Calmodulina/metabolismo , Linhagem Celular Tumoral , Citosol/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Canais Iônicos/efeitos dos fármacos , Canais Iônicos/metabolismo , Masculino , Modelos Biológicos , Fatores de Transcrição NFATC/metabolismo , Reação em Cadeia da Polimerase , Neoplasias da Próstata/metabolismo , Isoformas de Proteínas/metabolismo , Canais de Cátion TRPC/metabolismo , Canais de Cátion TRPV/metabolismo , Tapsigargina/metabolismo , Tapsigargina/farmacologia , Transcrição Gênica
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