Caspase Cascade Regulated Mitochondria Mediated Apoptosis in Monocrotophos Exposed PC12 Cells

Abstract

Monocrotophos (MCP) is a commonly used organophosphorus (OP) pesticide. We studied apoptotic changes in PC12 cells exposed to MCP. A significant induction in reactive oxygen species (ROS), lipid peroxide (LPO), and the ratio of glutathione disulfide (GSSG)/reduced glutathione (GSH) was observed in cells exposed to selected doses of MCP. Following the exposure of PC12 cells to MCP, the levels of protein and mRNA expressions of Caspase-3, Caspase-9, Bax, p53, P(21), Puma, and cytochrome-c were significantly upregulated, whereas the levels of Bcl(2), Bcl(w), and Mcl1 were downregulated. TUNEL assay, DNA laddering, and micronuclei induction show that long-term exposure of PC12 cells to MCP at higher concentration (10(-5) M) decreases the number of apoptotic events due to an increase in the number of necrotic cells. MCP-induced translocation of Bax and cytochrome-c proteins between the cytoplasm and mitochondria confirmed the role of p53 and Puma in mitochondrial membrane permeability. Mitochondria mediated apoptosis induction was confirmed by the increased activity of caspase cascade. We believe that this is the first report showing MCP-induced apoptosis in PC12 cells, which is mitochondria mediated and regulated through the caspase cascade. Our data demonstrates that MCP induced the apoptotic cell death in neuronal cells and identifies the possible cellular and molecular mechanisms of organophosphate pesticide-induced apoptosis in neuronal cells.

The association between ambient exposure to organophosphates and Parkinson's disease risk

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“…Mevinphos has been shown to disrupt oxidative phosphorylation by causing the dysfunction of complexes I through IV, which leads to cell death due to ATP depletion 35. Monocrotophos have also been shown to induce apoptosis in neurons and inhibit metabolism 34. Chlorpyrifos and chlorpyrifos-oxon exposure resulted in increased mitochondrial length, decreased number of mitochondria and decreased mitochondria movement in axon at concentrations that did not inhibit AChE 36.…”

Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research

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Oxidative Dna Damage Protective and Hepatoprotective Activity of Termi-Nalia Bellerica (Baheda)

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