Rotenone is an environmental neurotoxin that induces degeneration of dopaminergic neurons and the most common features of Parkinson's disease in animal models. It acts as a mitochondrial complex I inhibitor that impairs cellular respiration, with consequent increase of reactive oxygen species and oxidative stress. This study evaluates the rotenone-induced oxidative damage in PC12 cells, focusing particularly on protein oxidation. The identification of specific carbonylated proteins highlighted putative alterations of important cellular processes possibly associated with Parkinson's disease. Carbonylation of ATP synthase and of enzymes acting in pyruvate and glucose metabolism suggested a failure of mechanisms ensuring cellular energy supply. Concomitant oxidation of cytoskeletal proteins and of enzymes involved in the synthesis of neuroactive molecules indicated alterations of the neurotransmission system. Carbonylation of chaperon proteins as well as of proteins acting in the autophagy-lysosome pathway and the ubiquitin-proteasome system suggested the possible formation of cytosolic unfolded protein inclusions as result of defective processes assisting recovery/degradation of damaged molecules. In conclusion, this study originally evidences specific protein targets of rotenone-induced oxidative damage, suggesting some possible molecular mechanisms involved in rotenone toxicity.
Keywords: Oxidative stress; PC12 cells; Parkinsonism; Protein carbonylation; Rotenone.
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