Rosiglitazone protects human neuroblastoma SH-SY5Y cells against MPP+ induced cytotoxicity via inhibition of mitochondrial dysfunction and ROS production.
1-Methyl-4-phenylpyridinium ion (MPP(+)), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of intracellular reactive oxygen species (ROS) level and apoptotic death. Rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, has been known to show various non-hypoglycemic effects, including anti-inflammatory, anti-atherogenic, and anti-apoptotic. In the present study, we investigated the protective effects of rosiglitazone on MPP(+) induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as underlying mechanism. Our results suggested that the protective effects of rosiglitazone on MPP(+) induced apoptosis may be ascribed to its anti-oxidative properties, anti-apoptotic activity via inducing expression of SOD and catalase and regulating the expression of Bcl-2 and Bax. These data indicated that rosiglitazone might provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson's disease.
Jung
Tae Woo
TW
The Brain Korea 21 Project for Medical Science, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Lee
Ji Young
JY
Shim
Wan Sub
WS
Kang
Eun Seok
ES
Kim
Soo Kyung
SK
Ahn
Chul Woo
CW
Lee
Hyun Chul
HC
Cha
Bong Soo
BS
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics
C494826:BAX protein, human; D006540:Herbicides; D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D051028:bcl-2-Associated X Protein; D000077154:Rosiglitazone; D045304:Cytochromes c; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium