论文部分内容阅读
As a representative substance of the polycyclic aromatic hydrocarbons (PAH) , benzo[a]pyrene(B[a]P) is a widely distributed environmental contaminant.Exposure to B[a]P can take place by ingestion of contaminated (especially grilled, roasted or smoked) food or water, or inhalation of polluted air.Several studies have indicated that B[a]P exposure could impair learning and memory function on human population and animal models.Neuronal apoptosis plays a crucial role in neurodegenerative diseases manifesting deficits of learning and memory.In the present study, We utilized both in vivo and in vitro systems to demonstrate that B[a]P causes neuronal apoptosis.Using primary cortical neuronal culture, we showed for the first time that B[a]P administration results in elevation of expression of p25, p35 and cdk5 within the neuron thereby causing increase of cdk5 activity resulting in increased p53 phosphorylation at Ser15 from the cells.All these factors contributed to apopotic death of cortical neurons in vitro.When administered to SD rats, B[a]P was found to cause neuronal apoptosis and elevation of expression of p35, p25, cdk5 and Ser15 p53 phosphorylation in the cortex in a time and dose dependent manner.Our results show elevation of p-P53(S15) by Cdk5 contributes to cortical neuronal apoptosis after exposure to benzo[a]pyrene, implying that B[a]P may play a role in the neurodegenerative processes.