We previously demonstrated that the organochlorine pesticide dieldrin, a potential chemical risk factor for development of Parkinson's disease (PD), impairs mitochondrial function and promotes apoptosis in dopaminergic PC12 cells. We further demonstrated that caspase-3-dependent proteolytic activation of a member of the novel PKC family, protein kinase Cδ (PKCδ), contributes to apoptotic cell death in dopaminergic cells. In the present study, we report that the proapoptotic function of PKCδ can be regulated by overexpression of the mitochondrial anti-apoptotic protein Bcl2 in dieldrin-treated dopaminergic cells. Exposure to dieldrin (30 or 100 μM) for 3 h produced a dose-dependent increase in caspase-3 activation and DNA fragmentation in vector-transfected PC12 cells. Overexpression of human Bcl-2 in PC12 cells completely suppressed dieldrin-induced caspase-3 activation and DNA fragmentation. Furthermore, dieldrin-induced proteolytic activation of PKCδ was also remarkably reduced in Bcl-2-overexpressed cells. Together, these results suggest that the proapoptotic function of PKCδ can be regulated by mitochondrial redox modulators during neurodegenerative processes.
- Dopaminergic degeneration
- Environmental factors
- Oxidative stress
- Protein kinase C
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science