Ischemic heart disease is the main cardiovascular complication of diabetes patients which mainly caused by oxidative stress. DJ-1 is the key regulator for myocardial protection through inhibiting PTEN and activating Akt. This research is to investigate whether the antioxidant N-acetylcysteine (NAC) could alleviating diabetic myocardial ischemia reperfusion (I/R) injury by the protective molecule DJ-1. DJ-1 in rat myocardial H9c2 cells and cardiac tissue was respectively knocked down by siRNA and adeno-associated virus (AAV). From this study, it could be found that compared with high glucose (HG)-normal (N)/DM group, hypoxia reoxygenation (H/R) or I/R injury can aggravate oxidative stress injury and apoptosis rate of myocardial cells, inhibit the expression of Bcl-2, activate the BAX and cleaved caspase-3(c-caspase-3) protein and PTEN/Akt pathway. However, in the groups of HG-N, DM, HG-N+I/R and DM+I/R, NAC can significantly reduce oxidative stress injury and apoptosis rate of myocytes, promote the Bcl-2 and DJ-1 molecules, inhibit BAX and c-caspase-3 protein and PTEN/Akt pathway. Compared with HG-N+I/R+NAC and DM+I/R+NAC groups, the oxidative stress injury, apoptosis rate of myocardial cells and heart tissues increased after the knockdown of DJ-1, the expression of Bcl-2 and DJ-1 were inhibited, the BAX and c-caspase-3 expression was increased, and PTEN/Akt pathway was activated. Taken together, the findings suggest that NAC can reduce ischemia reperfusion injury in diabetic myocardium by up-regulating the PTEN/Akt pathway through the level of DJ-1.
Mechanism of N-acetylcysteine in alleviating diabetic myocardial ischemia reperfusion injury by regulating PTEN/Akt pathway through promoting DJ-1
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Wenyuan Li, Wei Li, Yan Leng, Yonghong Xiong, Rui Xue, Rong Chen, Zhongyuan Xia; Mechanism of N-acetylcysteine in alleviating diabetic myocardial ischemia reperfusion injury by regulating PTEN/Akt pathway through promoting DJ-1. Biosci Rep BSR20192118. doi: https://doi.org/10.1042/BSR20192118
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