Inhibitory effect of nicardipine on rotenone-induced apoptosis in SH-SY5Y human neuroblastoma cells
- Authors
- Park, Hae Jeong; Kim, Hak-Jae
- Issue Date
- Mar-2013
- Publisher
- Spandidos Publications
- Keywords
- nicardipine; rotenone; apoptosis; mitogen-activated protein kinase; caspase
- Citation
- Molecular Medicine Reports, v.7, no.3, pp 941 - 946
- Pages
- 6
- Journal Title
- Molecular Medicine Reports
- Volume
- 7
- Number
- 3
- Start Page
- 941
- End Page
- 946
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/13863
- DOI
- 10.3892/mmr.2013.1260
- ISSN
- 1791-2997
1791-3004
- 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 clownregulation of B-cell CLL/lymphoma 2 and upregulation of Bc12-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.
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