Isradipine prevents rotenone-induced intracellular calcium rise that accelerates senescence in human neuroblastoma SH-SY5Y cells.

Previous research demonstrated that rotenone (RT) induces neuronal injury partially by increasing intracellular Ca(2+) concentrations ([Ca(2+)]i), and inducing oxidative stress, leading to a neurodegenerative disorder. However, the mechanism of RT-induced injury remains elusive. Recent work revealed that Ca(2+) signaling is important for RT-induced senescence in human neuroblastoma SH-SY5Y cells. In the present study, we found that in SH-SY5Y cells, RT increased [Ca(2+)]i, senescence associated β-galactosidase activity, aggregation of lipofuscin, production of reactive oxygen species, G1/G0 cell cycle arrest, and activation of p53/p21 signaling proteins. In addition, RT decreased the expression of the signaling proteins for cell proliferation and survival, Cyclin-dependent kinase 2 (CDK2), cyclin D1, and Akt. Pretreatment of SH-SY5Y cells with isradipine, an L-type Ca(2+) channel blocker, or EGTA antagonized these effects of RT. These results suggested that application of isradipine might be a novel approach to prevent RT-induced neurodegenerative disorder such as Parkinson's disease.