Elevation of p-P53(S15) by cdk5 Contributes to neuronal apoptosis after exposure to benzo[a]pyrene

• 作 者: NIE Jisheng YAN Zhiwei DUAN Lei TANG Deliang NIU Qiao
• 机 构: Department of Occupational Health,School of Public Health,Shanxi Medical University,Taiyuan,Shanxi,C
• 出 处: 中国毒理学会第七次全国毒理学大会暨第八届湖北科技论坛
• 发表日期: 2015年9期
• 关键词: Benzo[a]pyrene neuronal apoptosis cdk5 p-P53(S15)

　　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.