RESUMO
LIM-homeodomain genes encode a major class of transcription factors which play a critical role in regulating tissue specific gene expression. In this report, we have shown that three members of the LIM-homeodomain gene family - Isl-1, Rlim and Lim-3 are expressed in adult rat sensory neurons. Furthermore, we show that the addition of nerve growth factor (NGF) to cultures of primary dorsal root ganglion neurons leads to the induction of Isl-1, Rlim and Lim-3 mRNA expression. The increase in Isl-1 mRNA levels upon NGF addition was rapid and occurred even in the presence of cycloheximide. These findings place Isl-1 as a novel member of the immediate early class of genes. In contrast, Rlim and Lim-3mRNA induction by NGF required protein synthesis. The role of LIM-homeodomain genes in mediating responses to NGF in adult sensory neurons is discussed.
Assuntos
Gânglios Espinais/fisiologia , Genes Precoces/genética , Proteínas de Homeodomínio/genética , Fator de Crescimento Neural/farmacologia , Neurônios Aferentes/fisiologia , Fatores Etários , Animais , Cicloeximida/farmacologia , Gânglios Espinais/citologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/fisiologia , Proteínas com Homeodomínio LIM , Proteínas do Tecido Nervoso/genética , Neurônios Aferentes/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , RNA Mensageiro/análise , Ratos , Proteínas Repressoras/genética , Fatores de Transcrição , Ubiquitina-Proteína LigasesAssuntos
Regulação Viral da Expressão Gênica , Neurônios Aferentes/virologia , Simplexvirus/fisiologia , Animais , Sequência de Bases , Linhagem Celular , Células Cultivadas , Cloranfenicol O-Acetiltransferase/genética , Humanos , Proteínas Imediatamente Precoces/genética , Neurônios Aferentes/citologia , Regiões Promotoras Genéticas , Simplexvirus/genética , TransfecçãoRESUMO
The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on hepatic bile formation was studied in isolated perfused rat livers and rat hepatocytes. Studies in isolated perfused rat livers showed that infusion of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 3 micromol/min or 100 microM) 1) increased bile flow without affecting biliary excretion of simultaneously infused taurocholate, 2) increased biliary concentration and excretion of HCO3(-) but did not affect biliary excretion of glutathione, and 3) increased net perfusate H+ efflux without affecting hepatic O2 uptake. Studies in isolated rat hepatocytes showed that 1) 8-BrcGMP increased intracellular pH in the presence (but not in the absence) of extracellular HCO-3, and effect inhibited by 4,4' -diisothiocyanostilbene-2,2'-disulfonic acid and Na+ replacement, 2) 8-BrcGMP did not affect taurocholate uptake and intracellular [Ca2+], and 3) bile acids, like ursodeoxycholate and cholate, did not increase cellular cGMP. Taken together, these results indicate that cGMP stimulates bile acid-independent bile formation, in part by stimulating biliary HCO3- excretion. cGMP may increase HCO3- excretion by stimulating sinusoidal Na+ - HCO3- cotransport, but not Na+/H+ exchange. cGMP, unlike adenosine 3',5'-cyclic monophosphate, may not regulate hepatic taurocholate transport, and bile acid-induced HCO3- rich choleresis may not be mediated via cGMP.
