title: Rosiglitazone protects human neuroblastoma SH-SY5Y cells against MPP+ induced cytotoxicity via inhibition of mitochondrial dysfunction and ROS production.
abstract: 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.
authors.affiliation: The Brain Korea 21 Project for Medical Science, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Jung
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Wan Sub
authors.initials: WS
authors.lastname: Shim
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Kim
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Ahn
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Cha
mesh_terms: 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
chemical_list: 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