title: Monocrotophos induced apoptosis in PC12 cells: role of xenobiotic metabolizing cytochrome P450s.
abstract: Monocrotophos (MCP) is a widely used organophosphate (OP) pesticide. We studied apoptotic changes and their correlation with expression of selected cytochrome P450s (CYPs) in PC12 cells exposed to MCP. A significant induction in reactive oxygen species (ROS) and decrease in glutathione (GSH) levels were observed in cells exposed to MCP. Following the exposure of PC12 cells to MCP (10(-5) M), the levels of protein and mRNA expressions of caspase-3/9, Bax, Bcl(2), P(53), P(21), GSTP1-1 were significantly upregulated, whereas the levels of Bclw, Mcl1 were downregulated. A significant induction in the expression of CYP1A1/1A2, 2B1/2B2, 2E1 was also observed in PC12 cells exposed to MCP (10(-5) M), whereas induction of CYPs was insignificant in cells exposed to 10(-6) M concentration of MCP. We believe that this is the first report showing altered expressions of selected CYPs in MCP-induced apoptosis in PC12 cells. These apoptotic changes were mitochondria mediated and regulated by caspase cascade. Our data confirm the involvement of specific CYPs in MCP-induced apoptosis in PC12 cells and also identifies possible cellular and molecular mechanisms of organophosphate pesticide-induced apoptosis in neuronal cells.
authors: Indian Institute of Toxicology Research, Lucknow, India.
authors: Mahendra Pratap
authors: MP
authors: Kashyap
authors: Abhishek Kumar
authors: AK
authors: Singh
authors: Vivek
authors: V
authors: Kumar
authors: Vinay Kumar
authors: VK
authors: Tripathi
authors: Ritesh Kumar
authors: RK
authors: Srivastava
authors: Megha
authors: M
authors: Agrawal
authors: Vinay Kumar
authors: VK
authors: Khanna
authors: Sanjay
authors: S
authors: Yadav
authors: Swatantra Kumar
authors: SK
authors: Jain
authors: Aditya Bhushan
authors: AB
authors: Pant
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D007306:Insecticides / Q000494:pharmacology*; D008999:Monocrotophos / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D007306:Insecticides; D017382:Reactive Oxygen Species; D015262:Xenobiotics; D008999:Monocrotophos; D005978:Glutathione