Possible involvement of Ca2+ signaling in rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells.
Rotenone, an inhibitor of mitochondrial respiratory chain complex I, is a useful tool to elicit animal model of Parkinson's disease. Rotenone-induced neuronal apoptosis may contribute to the etiology of Parkinson's disease. However, the mechanism of rotenone-induced apoptosis is not fully understood. In the present study, we show that Ca2+ signaling is essential for rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells. By using Fluo-3/AM and Fura-2/AM, the fluorescent calcium indicator, rotenone was found to cause a rise in intracellular free Ca2+ ([Ca2+]i). The intracellular Ca2+ chelator BAPTA attenuated rotenone-induced apoptosis. Notably, Ca2+ suppression also prevented rotenone-induced apoptotic related events including reactive oxygen species production, G2/M cell cycle arrest and caspase activation, suggesting that Ca2+ signaling is upstream to these events. In the absence of extracellular Ca2+, the rotenone-induced [Ca2+]i elevation was inhibited. Further, the voltage-dependent Ca2+ channel blocker nifedipine suppressed most of the elevation of [Ca2+]i induced by rotenone. These results demonstrate that rotenone leads to an elevation in [Ca2+]i through Ca2+ influx by the opening of voltage-gated Ca2+ channel. This study of rotenone may help to elucidate the neurodegenerative mechanims in Parkinson's disease.
Wang
Xin-Jian
XJ
Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Xu
Jian-Xing
JX
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020169:Caspases / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010300:Parkinson Disease / Q000209:etiology / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014475:Uncoupling Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; D012402:Rotenone; D004533:Egtazic Acid; D020169:Caspases; D009543:Nifedipine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium