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: Tae Woo Jung, Ji Young Lee, Wan Sub Shim, Eun Seok Kang, Soo Kyung Kim, Chul Woo Ahn, Hyun Chul Lee, Bong Soo Cha
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 253 Issue 1-2 Pg. 53-60 (Feb 15 2007) ISSN: 0022-510X [Print] Netherlands
• PMID: 17266988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAX protein, human
• Herbicides
• Hypoglycemic Agents
• Neuroprotective Agents
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• Reactive Oxygen Species
• Thiazolidinediones
• bcl-2-Associated X Protein
• Rosiglitazone
• Cytochromes c
• Caspase 3
• 1-Methyl-4-phenylpyridinium

Topics

• 1-Methyl-4-phenylpyridinium (toxicity)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cytochromes c (metabolism)
• Herbicides (toxicity)
• Humans
• Hypoglycemic Agents (pharmacology)
• Mitochondria (drug effects, metabolism)
• Neuroblastoma
• Neurons (cytology, drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• RNA, Messenger (metabolism)
• Reactive Oxygen Species (metabolism)
• Rosiglitazone
• Thiazolidinediones (pharmacology)
• bcl-2-Associated X Protein (genetics)