OBJECTIVE: Phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway plays an important role in regulating cell survival, apoptosis and oxidative stress (OS). Phosphatase and tensin homolog deleted on chromosome ten (PTEN) can negatively regulate PI3K/AKT signaling pathway. DJ-1 is also a key negative regulator of PTEN. DJ-1-PTEN/PI3K/AKT signaling pathway regulates ischemia reperfusion (I-R). This study investigated the role of DJ-1 in affecting myocardial I-R injury.
MATERIALS AND METHODS: The rat myocardial I-R injury model was established. Expression of DJ-1 and PTEN in myocardial tissue was detected. The reactive oxidative species (ROS) content was detected using flow cytometry. Caspase-3 activity, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activities were determined by ultraviolet spectrophotometry. Rat cardiomyocytes H9C2 were cultured in vitro and divided into control group, I-R group, I-R+pIRES2-NC group, and I-R+pIRES2-DJ-1 group. Levels of DJ-1, PTEN and phosphorylated AKT (p-AKT) were detected. Cell apoptosis and ROS content were evaluated using flow cytometry.
RESULTS: Compared with sham group, caspase-3 activity, MDA content, and PTEN expression were significantly increased, while SOD activity and DJ-1 levels were significantly reduced in myocardial tissue of I-R group (p<0.05). Compared with the control, I-R treatment markedly induced H9C2 cell apoptosis, decreased DJ-1 and p-AKT expression, and enhanced ROS production and PTEN expression. DJ-1 overexpression apparently down-regulated PTEN expression, elevated p-AKT level, and attenuated apoptosis and ROS production in H9C2 cells (p<0.05).
CONCLUSIONS: Abnormal expression of DJ-1 plays a regulatory role in the process of myocardial I-R injury. Over-expression of DJ-1 can reduce myocardial cell I-R damage sensitivity by inhibiting PTEN expression, enhancing the activity of PI3K/AKT signaling pathway, reducing ROS production, and alleviating apoptosis.Free PDF Download
To cite this article
L.-H. Xin, W.-J. Liu, T. Song, L. Zhang
Overexpression of DJ-1 expression protects cardiomyocyte apoptosis induced by ischemia reperfusion
Eur Rev Med Pharmacol Sci
Vol. 23 - N. 4