Anti-apoptotic actions of PPAR-gamma against ischemic stroke.
Stroke is a leading cause of adult disability and mortality. Diabetes is a major risk factor for stroke. Patients with diabetes have a higher incidence of stroke and a poorer prognosis after stroke. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand-modulated transcriptional factor and a therapeutic target for treating type II diabetes. It is well-documented that activation of PPAR-gamma can also attenuate postischemic inflammation and damage. In this review, we focus on the newly revealed anti-apoptotic actions of PPAR-gamma against cerebral ischemia. PPAR-gamma, by increasing superoxide dismutase/catalase and decreasing nicotinamide adenine dinucleotide phosphate oxidase levels, attenuated ischemia-induced reactive oxygen species and subsequently alleviated the postischemic degradation of Bcl-2, Bcl-xl, and Akt. The preserved Akt phosphorylated Bad. Meanwhile, PPAR-gamma also promotes the transcription of 14-3-3epsilon. Elevated 14-3-3epsilon binds and sequesters p-Bad and prevents Bad translocation to neutralize the anti-apoptotic function of Bcl-2. This review further supports the notion that PPAR-gamma may serve as a potential therapeutic target for treating ischemic stroke.
Fong
Wen-Hsuan
WH
Neuroscience Division, Institute of Biomedical Sciences, Academia Sinica, Rm 404, Taipei, Taiwan, Republic of China.
Tsai
Hsin-Da
HD
Chen
Yu-Chang
YC
Wu
Jui-Sheng
JS
Lin
Teng-Nan
TN
D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008024:Ligands; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000077154:Rosiglitazone; D020521:Stroke / Q000503:physiopathology* / Q000628:therapy; D045162:Thiazolidinediones / Q000627:therapeutic use; D051025:bcl-Associated Death Protein / Q000378:metabolism
D048948:14-3-3 Proteins; D007004:Hypoglycemic Agents; D008024:Ligands; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D045162:Thiazolidinediones; C482983:YWHAE protein, human; D051025:bcl-Associated Death Protein; D000077154:Rosiglitazone; D051057:Proto-Oncogene Proteins c-akt