Background: Mutations in Parkin have been reported to cause Parkinson’s disease (PD). In addition, experimental studies have shown that chronic systemic exposure of rotenone, a mitochondrial complex I inhibitor, results in the development of PD in animal models.
Aim: To investigate the susceptibility of human olfactory cell cultures with parkin mutations to rotenone exposure.
Methods: Primary cultures of human olfactory epithelium derived from patients with heterozygous mutations in the parkin gene were exposed to increasing doses of rotenone for 24, 48 and 72 hours, and cell death was determined using LDH and MTT assays.
Results: Chronic exposure to low dose rotenone caused morphological change in all treated cell lines. However, there was no morphological difference between the control and the parkin mutated cells following rotenone exposure. Rotenone did not cause significant cell death during the 24-48 hours exposure period but dose-dependent cell death was observed following 72 hours of rotenone exposure. Cell lines with compound heterozygous parkin mutations were more susceptible to cell death when compared to wild-type and single heterozygous parkin mutated cell lines.
Conclusion: Rotenone causes dose-dependent cell death in human-derived olfactory stem cells with compound heterozygous mutations of parkin gene. Only compound heterozygous parkin mutations lead to vulnerability to cell death induced by rotenone exposure in this cell model.