Journal of pineal research
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Melatonin is a potent scavenger of reactive oxygen species and a strong antioxidant. Melatonin exerts protective effects against damage by the enhancing the Akt signal pathway, thus regulating apoptotic cell death. Akt phosphorylates pro-apoptotic proteins such as Bad and FoxO1 and inhibits the pro-apoptotic functions of these proteins. ⋯ However, melatonin prevented hepatic I/R injury-induced decreases in these proteins levels. Moreover, the interaction levels between phospho-Bad and 14-3-3 and between phospho-FoxO1 and 14-3-3 are reduced in vehicle-treated animals, and melatonin attenuated decreases in the binding levels of these proteins. 14-3-3 exerts an anti-apoptotic function by sequestration of Bad and FoxO1. These findings suggest that melatonin exerts protective effects in case of hepatic I/R damage by maintaining the binding of phospho-Bad and 14-3-3 and the binding of phospho-FoxO1 and 14-3-3, thus preventing activation of apoptotic cell death.