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

Abstract

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.

• Authors: X Yu, X Li, G Jiang, X Wang, H C Chang, W H Hsu, Qinglin Li
• Journal: Neuroscience (Neuroscience) Vol. 246 Pg. 243-53 (Aug 29 2013) ISSN: 1873-7544 [Electronic] United States
• PMID: 23664925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 IBRO. All rights reserved.

Chemical References

• Rotenone
• Calcium
• Isradipine

Topics

• Calcium (metabolism)
• Cell Line, Tumor
• Cellular Senescence (drug effects, physiology)
• Humans
• Intracellular Fluid (drug effects, metabolism)
• Isradipine (pharmacology)
• Neuroblastoma (metabolism)
• Rotenone (antagonists & inhibitors, toxicity)
• Time Factors