Aims It has been shown that Ndrg2 (N-Myc downstream-regulated gene 2), a Myc-repressed gene, is markedly expressed in heart. Ndrg2 can act as a stress responsor under hypoxia and is necessary for hypoxia-induced apoptosis in certain tumour cell lines. In the present study, we investigated whether ischaemia/reperfusion (I/R) injury played a role in the regulation of Ndrg2 expression in rat heart and further explored the possible relationship between Ndrg2 expression and cardiomyocyte apoptosis induced by I/R injury.
Methods Rats were subjected to open chest surgery coronary artery ligation for ischaemia only or followed by reperfusion. Immunostaining and Western blot were applied to test the expression of Ndrg2, c-Myc, cleaved-caspase3 from myocardium, and TUNEL (terminal dUTP nick end labelling)-staining for apoptosis determination of myocardium.
Results The immunostaining confirmed Ndrg2 distribution in cardiomyocytes. The Ndrg2 expression in myocardial tissue after I/R injury was significantly reduced at both mRNA and protein levels. We also observed that expression of c-Myc can be increased by I/R injury and was significantly inversely correlated with Ndrg2 expression. Furthermore, the rapid apoptotic rate at the early phase of reperfusion was ameliorated in the late phase. Some results in vivo were further confirmed by ex vivo study in cultured cardiomyocytes subjected to simulated I/R.
Conclusions Our data suggests that up-regulation of pro-apoptotic c-Myc expression induced by I/R injury in rat myocardium may contribute to the down-regulation of also pro-apoptotic Ndrg2. Such stress response may be involved in the post I/R anti-apoptosis mechanism and myocardial repair in rat.