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Monocrotophos Induced Apoptosis in PC12 Cells: Role of Xenobiotic Metabolizing Cytochrome P450s

By Mahendra Pratap Kashyap, Abhishek Kumar Singh, Vivek Kumar, Vinay Kumar Tripathi, Ritesh Kumar Srivastava, Megha Agrawal, Vinay Kumar Khanna, Sanjay Yadav, Swatantra Kumar Jain and Aditya Bhushan Pant


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, Bcl2, P53, P21, 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

Topics: Research Article
Publisher: Public Library of Science
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Provided by: PubMed Central

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  29. (2009). Melatonin prevents damage elicited by the organophosphorous pesticide diazinon on the mouse testis.
  30. (2007). Mitochondrial membrane permeabilization in cell death.
  31. (2009). Mitochondrial membrane permeabilization in neuronal injury.
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