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.