INESCAPABLE STRESS INDUCES CYTOSKELETON DAMAGE THROUGH INCREMENT IN LIPID PEROXIDATION AND GSK-3ß ACTIVATION

MIGUEZ, J; PEIXOTO, E; FERRERO, A; CERESETO, M; SIFONIOS, L; GUELMAN, L; WIKINSKI, S.

Buenos Aires, Argentina

Congreso; XXXVII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2005

Sociedad Argentina de Farmacología Experimental

Inescapable stress (IS) induces a decrement in the light neurofilament subunit (NFL) in the hippocampus, probably linked to the dendritic atrophy observed in experimental models of depression. NFL reduction could be due to either increased oxidative stress or the hyperphosphorylation of cytoskeleton proteins by glycogen synthase kinase 3â (GSK-3â), leading to proteolysis. We explored these mechanisms in rats exposed to IS. Adult rats were exposed to 60 inescapable foot shocks (0.6 mA, 15 sec). Controls did not receive IS. One hour or 4 days later, lipid peroxidation and total glutathione (GSH) were employed as parameters of oxidative stress. Cytoskeleton hyperphosphorylation was estimated by Western blot analysis of â-catenin level, a substrate of GSK-3â. One hour after the IS an increment in lipid peroxidation (22%, p < 0.05 vs control) and a decrement in the â- catenin level (49%, p < 0.05 vs control) were observed, but no modification in total GSH or GSK-3â levels were found. Four days after the stress only â-catenin levels remained decreased (19%, p < 0.05 vs control). Our results provide preliminary evidences supporting the hypothesis that oxidative stress and GSK-3â activation could be involved in the cytoskeleton damage observed after IS.â (GSK-3â), leading to proteolysis. We explored these mechanisms in rats exposed to IS. Adult rats were exposed to 60 inescapable foot shocks (0.6 mA, 15 sec). Controls did not receive IS. One hour or 4 days later, lipid peroxidation and total glutathione (GSH) were employed as parameters of oxidative stress. Cytoskeleton hyperphosphorylation was estimated by Western blot analysis of â-catenin level, a substrate of GSK-3â. One hour after the IS an increment in lipid peroxidation (22%, p < 0.05 vs control) and a decrement in the â- catenin level (49%, p < 0.05 vs control) were observed, but no modification in total GSH or GSK-3â levels were found. Four days after the stress only â-catenin levels remained decreased (19%, p < 0.05 vs control). Our results provide preliminary evidences supporting the hypothesis that oxidative stress and GSK-3â activation could be involved in the cytoskeleton damage observed after IS.â-catenin level, a substrate of GSK-3â. One hour after the IS an increment in lipid peroxidation (22%, p < 0.05 vs control) and a decrement in the â- catenin level (49%, p < 0.05 vs control) were observed, but no modification in total GSH or GSK-3â levels were found. Four days after the stress only â-catenin levels remained decreased (19%, p < 0.05 vs control). Our results provide preliminary evidences supporting the hypothesis that oxidative stress and GSK-3â activation could be involved in the cytoskeleton damage observed after IS.â. One hour after the IS an increment in lipid peroxidation (22%, p < 0.05 vs control) and a decrement in the â- catenin level (49%, p < 0.05 vs control) were observed, but no modification in total GSH or GSK-3â levels were found. Four days after the stress only â-catenin levels remained decreased (19%, p < 0.05 vs control). Our results provide preliminary evidences supporting the hypothesis that oxidative stress and GSK-3â activation could be involved in the cytoskeleton damage observed after IS.â- catenin level (49%, p < 0.05 vs control) were observed, but no modification in total GSH or GSK-3â levels were found. Four days after the stress only â-catenin levels remained decreased (19%, p < 0.05 vs control). Our results provide preliminary evidences supporting the hypothesis that oxidative stress and GSK-3â activation could be involved in the cytoskeleton damage observed after IS.â levels were found. Four days after the stress only â-catenin levels remained decreased (19%, p < 0.05 vs control). Our results provide preliminary evidences supporting the hypothesis that oxidative stress and GSK-3â activation could be involved in the cytoskeleton damage observed after IS.â-catenin levels remained decreased (19%, p < 0.05 vs control). Our results provide preliminary evidences supporting the hypothesis that oxidative stress and GSK-3â activation could be involved in the cytoskeleton damage observed after IS.â activation could be involved in the cytoskeleton damage observed after IS.