Resumen

Evidence suggest that hydrogen peroxide (H2O2) plays an important role in the signal transduction cascade involved in cellular apoptosis. It is also known that c-Jun N-terminal kinase (JNK) regulates apoptosis and cellular proliferation. We decided to establish the contribution of the JNK pathway to astrocyte apoptosis induced by H2O2 and to study its prevention by different antioxidants. In incubations with different H2O2 concentrations (0.2 – 1.0 mM), an increase of 45% in ROS formation was observed. In 3h incubations with 500 mM H2O2, apoptotic astrocytes were detected by Hoechst 33258 dye staining, being this apoptotic mechanism prevented by 3h preincubation with 100 mM melatonin. Caspase-3-specific activity increased up to 120% after 3h incubations with 500 mM H2O2 whereas a decrease of 25% was measured when the astrocytes were preincubated with 100 mM melatonin. Under these conditions, we detected JNK activation through Western blots, which was prevented by different antioxidants, such as GSH, NAC and catalase, but not by 100 mM melatonin. On the other hand, 100 mM melatonin decreased H2O2– induced Bax levels detected through Western blots. Our results suggest that melatonin prevents H2O2-induced apoptosis involving a Bax-mediated mechanism. However, other antioxidants such as GSH, NAC and catalase, were able to prevent the increased JNK phosphorylation, activated as a consequence of oxidative stress. Supported by grants from UBA (TX-36) and CONICET (PEI 089).

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2007-01-31   |   1,047 visitas   |   Evalua este artículo 0 valoraciones

Vol. 1 Núm.1. Abril 2002 Pags. Qviva 2002; 1(1)