title: Inhibitory effect of nicardipine on rotenone‑induced apoptosis in SH‑SY5Y             human neuroblastoma cells.
abstract: Previous studies have demonstrated that calcium channel blockers have protective             effects on damaged brains. In the present study, the protective effect of the             calcium channel blocker nicardipine against rotenone‑induced apoptosis in SH‑SY5Y             human neuroblastoma cells was investigated, focusing on mitogen‑activated protein             kinases (MAPKs) and caspase (CASP)‑mediated apoptotic events. Nicardipine was             found to decrease rotenone‑induced apoptosis through 4,6‑diamidino‑2‑phenylindole             staining and the terminal deoxynucleotidyl transferase‑mediated dUTP nick end‑labeling             assay. In addition, nicardipine was identified to inhibit rotenone‑induced elevation             of intracellular Ca2+ concentration measured using the Fluo‑4 AM fluorescent dye.             Rotenone increased phosphorylation of c‑Jun NH2‑terminal kinase (JNK) and p38             MAPK, whereas nicardipine blocked these increases. Nicardipine also prevented             downregulation of B‑cell CLL/lymphoma 2 and upregulation of Bcl2‑associated X             protein by rotenone. Furthermore, nicardipine abrogated cleavage of CASP9 and             3 and poly (ADP‑ribose) polymerase‑1 by rotenone and CASP3 enzyme activity in             rotenone‑treated cells. These results indicate that nicardipine exerts a protective             effect against rotenone‑induced apoptosis in SH‑SY5Y cells, inhibiting phosphorylation             of JNK and p38 MAPK and activation of CASPs.
authors.affiliation: Kohwang Medical Research Institute, School of Medicine, Kyung                     Hee University, Seoul, Republic of Korea.
authors.forename: Hae Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Hak-Jae
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009447:Neuroblastoma; D009529:Nicardipine / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D015854:Up-Regulation / Q000187:drug effects; D014966:Xanthenes / Q000737:chemistry; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D002121:Calcium Channel Blockers; C409648:Fluo 4; D007306:Insecticides; D019253:Proto-Oncogene Proteins c-bcl-2; D014966:Xanthenes; D051028:bcl-2-Associated X Protein; D012402:Rotenone; D009529:Nicardipine; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9; D002118:Calcium