Celastrol from 'Thunder God Vine' protects SH-SY5Y cells through the preservation of mitochondrial function and inhibition of p38 MAPK in a rotenone model of Parkinson's disease.
Celastrol, a potent natural triterpene and one of the most promising medicinal molecules, is known to possess a broad range of biological activity. Rotenone, a pesticide and complex I inhibitor, is commonly used to produce experimental models of Parkinson's disease both in vivo and in vitro. The present study was designed to examine the effects of celastrol on cell injury induced by rotenone in the human dopaminergic cells and to elucidate the possible mechanistic clues in its neuroprotective action. We demonstrate that celastrol protects SH-SY5Y cells from rotenone-induced cellular injury and apoptotic cell death. Celastrol also prevented the increased generation of reactive oxygen species and mitochondrial membrane potential (ΔΨm) loss induced by rotenone. Similarly, celastrol treatment inhibited cytochrome c release, Bax/Bcl-2 ratio changes, and caspase-9/3 activation. Celastrol specifically inhibited rotenone-evoked p38 mitogen-activated protein kinase activation in SH-SY5Y cells. These data suggest that celastrol may serve as a potent agent for prevention of neurotoxin-induced neurodegeneration through multiple mechanisms and thus has therapeutic potential for the treatment of neurodegenerative diseases.
Department of Biotechnology, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju, 501-759, Republic of Korea.
Bong-Suk
BS
Choi
Hyool
H
Kim
Hyo Jeong
HJ
Lee
Kumar
K
Sapkota
Se Eun
SE
Park
Seung
S
Kim
Sung-Jun
SJ
Kim
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000503:physiopathology*; D053978:Pentacyclic Triterpenes; D012402:Rotenone / Q000037:antagonists & inhibitors / Q000633:toxicity*; D014315:Triterpenes / Q000627:therapeutic use*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D018696:Neuroprotective Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D012402:Rotenone; D048051:p38 Mitogen-Activated Protein Kinases; C050414:celastrol