title: 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.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei 230038, China.
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Jiang
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: H C
authors.initials: HC
authors.lastname: Chang
authors.forename: W H
authors.initials: WH
authors.lastname: Hsu
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Li
mesh_terms: D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D017275:Isradipine / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism*; D012402:Rotenone / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013997:Time Factors
chemical_list: D012402:Rotenone; D002118:Calcium; D017275:Isradipine