Dysfunction and apoptosis of neurons triggered by various stimulations mainly contribute to neurodegenerative diseases. Gradually appeared reports have indicated that stimulations can initiate activation of aberrant c...
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Dysfunction and apoptosis of neurons triggered by various stimulations mainly contribute to neurodegenerative diseases. Gradually appeared reports have indicated that stimulations can initiate activation of aberrant cell cycle factors in neurons, leading to abnormal cell behavior and apoptosis finally. In our study, apoptosis induced by activation of cell cycle factors was investigated using mice and PC12 cells as acute alcohol exposure models in vivo and in vitro, respectively. Moreover, p53 inhibitor and CDK4 inhibitor were applied in alcohol-treated PC12 cells to define the essential roles of p53, cyclin D1 and CDK4 in caspase-3 apoptotic pathway upon acute alcohol exposure. The data showed that acute excessive alcohol exposure up-regulated the expressions of p53, CDK4 and cyclin D1, and it also triggered apoptosis. However, chronic consumption of low content of alcohol did not cause neuronal apoptosis. Inhibition of p53 weakened the activation of caspase-3 and attenuated alcohol-induced apoptosis in PC12 cells, whereas blockage of cyclin D1 and CDK4 did not have such an effect. Blockage of p53/caspase-3 pathway would give cells time to metabolize alcohol and repair alcohol-caused damage. Taken together, neuronal apoptosis triggered by acute excessive alcohol exposure was correlated to activation of the p53/caspase-3 signaling, and blockage of p53 would be a possible way to suppress acute alcohol exposure-induced apoptosis.
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