|Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway|
|Zhang, Xue-Jiao1; Xiong, Zi-Bo2; Tang, An-Li1; Ma, Hong1; Ma, Yue-Dong1; Wu, Jing-Guo1; Dong, Yu-Gang1|
|关键词||Akt ischaemia myocardial infarction peroxisome proliferator-activated receptor gamma phosphatidylinositol 3-kinase rosiglitazone|
|刊名||CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY|
|WOS标题词||Science & Technology|
|类目[WOS]||Pharmacology & Pharmacy ; Physiology|
|研究领域[WOS]||Pharmacology & Pharmacy ; Physiology|
|关键词[WOS]||ACTIVATED-RECEPTOR-GAMMA ; GLYCOGEN-SYNTHASE KINASE-3-BETA ; CARDIOMYOCYTES IN-VITRO ; K-ATP CHANNELS ; ISCHEMIA/REPERFUSION INJURY ; PPAR-GAMMA ; 3-KINASE PATHWAY ; CELL-SURVIVAL ; APOPTOSIS ; HEART|
1. Rosiglitazone is widely used in the treatment of Type 2 diabetes. However, in recent years it has become evident that the therapeutic effects of peroxisome proliferator-activated receptor gamma ligands reach far beyond their use as insulin sensitizers. Recently, the ability of rosiglitazone pretreatment to induce cardioprotection following ischaemia-reperfusion (I/R) has been well documented; however, the protective mechanisms have not been elucidated. In the present study, examined the role of the phosphatidylinositol 3-kinase (PI3-K)/Akt signalling pathway in rosiglitazone cardioprotection following I/R injury.
2. Mice were pretreated with 3 mg/kg per day rosiglitazone for 14 days before hearts were subjected to ischaemia (30 min) and reperfusion (2 h). Wortmannin (1.4 mg/kg, i.p.), an inhibitor of PI3-K, was administered 10 min prior to myocardial I/R. Then, activation of the PI3-K/Akt/glycogen synthase kinase (GSK)-3 alpha signalling pathway was examined. The effects of PI3-K inhibition on rosiglitazone-induced cardioprotection were also evaluated.
3. Compared with control rats, the ratio of infarct size to ischaemic area (area at risk) and the occurrence of sustained ventricular fibrillation in rosiglitazone-pretreated rats was significantly reduced (P < 0.05). Rosiglitazone pretreatment attenuated cardiac apoptosis, as assessed by ELISA to determine cardiomyocyte DNA fragmentation. Rosiglitazone pretreatment significantly increased levels of phosphorylated (p-) Akt and p-GSK-3 alpha in the rat myocardium. Pharmacological inhibition of PI3-K by wortmannin markedly abolished the cardioprotection induced by rosiglitazone.
4. These results indicate that rosiglitazone-induced cardioprotection in I/R injury is mediated via a PI3-K/Akt/GSK-3 alpha-dependent pathway. The data also suggest that modulation of PI3-K/Akt/GSK-3 alpha-dependent signalling pathways may be a viable strategy to reduce myocardial I/R injury.
|作者单位||1.Sun Yat Sen Univ, Affiliated Hosp 1, Dept Cardiol, Guangzhou 510080, Guangdong, Peoples R China|
2.Peking Univ, Shenzhen Hosp, Div Renal, Shenzhen, Guangdong, Peoples R China
|Zhang, Xue-Jiao,Xiong, Zi-Bo,Tang, An-Li,et al. Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway[J]. CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY,2010,37(2):156-161.|
|APA||Zhang, Xue-Jiao.,Xiong, Zi-Bo.,Tang, An-Li.,Ma, Hong.,Ma, Yue-Dong.,...&Dong, Yu-Gang.(2010).Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway.CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY,37(2),156-161.|
|MLA||Zhang, Xue-Jiao,et al."Rosiglitazone-induced myocardial protection against ischaemia-reperfusion injury is mediated via a phosphatidylinositol 3-kinase/Akt-dependent pathway".CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY 37.2(2010):156-161.|