RESUMO
Besides its effect regarding addiction, ethanol also damages the central nervous system when it is used at high doses for a long time. The increase in the activity of Rho/Rho kinase pathway leads to central nervous system pathologies such as cerebral injury and epileptogenesis. The aim of this study was to investigate the contribution of Rho/Rho Kinase pathway to the degenerative and addictive effects of ethanol. For this purpose, we determined the Rho-kinase activity in striatum and hippocampus of rat brain. Wistar rats were treated with ethanol in a special liquid diet for 21 days. An isocaloric liquid diet without ethanol was given to the rats in the control group during the study. At the end of the 21 day ethanol exposure, one group was kept on taking ethanol and another group was withdrawn from ethanol. The rats were decapitated and their brains were taken out. Striatum and hippocampus were isolated. Phospho-moesin protein levels were measured in striatum and hippocampus homogenates using by Western blot analysis. The Rho-kinase (ROCK) activity in the striatum was found to be significantly decreased in ethanol exposed rats. In the hippocampus, there was a significant increase in the ROCK activity in the ethanol group. Our results indicated that ethanol caused some significant changes in Rho/Rho Kinase pathway in rat brain (Fig. 2, Ref. 25).
Assuntos
Corpo Estriado/enzimologia , Etanol/administração & dosagem , Hipocampo/enzimologia , Síndrome de Abstinência a Substâncias/enzimologia , Quinases Associadas a rho/metabolismo , Animais , Corpo Estriado/química , Corpo Estriado/efeitos dos fármacos , Etanol/toxicidade , Hipocampo/química , Hipocampo/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Síndrome de Abstinência a Substâncias/etiologiaRESUMO
OBJECTIVE: Effect of estrogenic compounds and 17ß-estradiol (E2), which induces endothelial cell motility, was investigated on ROCK-2 expression in rat coronary vascular endothelial cells (CVEC). METHODS: The CVEC were isolated from the heart of Wistar rats by collagenase (0.04%) and incubated with E2 (1-100 nM), estrogen receptor α (ERα) agonist: propyl pyrazole triol (PPT, 10 nM); ERß agonists: (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN, 10 nM) and E2-conjugate with bovine serum albumin (E2-BSA, 1 nM); and GPER1 agonist: G1 (100 nM). Furthermore, the effect of combination of E2 with estrogen receptors (ERs) antagonist and GPER1 agonist, ICI-182780 (10 µM), physiological estrogen antagonists: progesterone (P4, 10-100 nM) and testosterone (T, 10-100 nM); transcription inhibitor: actinomycin-D (1 µg/ml); GPER1 antagonist: G-15 (100 nM), superoxide dismutase, (SOD, 500 U/ml); Gi/o protein inhibitor: pertussis toxin (PTX, 100 µg/ml); and epidermal growth factor receptor (EGFR) blocker: AG-1478 (10 µM) was tested. After 24h incubation, ROCK-2 and GPER1 protein expressions were detected in the CVEC by Western-blotting. RESULTS: E2, ICI-182780, and G1 but not E2-BSA significantly up-regulated ROCK-2 expression, which was suppressed by actinomycin-D, PTX, AG-1478, and G-15. However, PPT and DPN had no effects on the ROCK-2 expression. ICI-182780, P4, T or SOD did not antagonize the E2 action. GPER1 expression was demonstrated in the CVEC. CONCLUSIONS: Estrogens could up-regulate ROCK-2 in the rat CVEC through GPER1 and EGFR transactivation.
