Role of Bcl-2 family members in 4-hydroxynonenal (HNE) mediated apoptosis

Abstract

4-Hydroxynonenal (HNE), a very reactive lipid peroxidation product, was shown to induce oxidative stress and apoptosis in a dose-dependent manner in a variety of cells Our recent data showed that FINE triggered caspase-9 and 3 activation and PARP cleavage in monocytic cell line U937. Following 10 mu M HNE treatment, levels of phosphorylated JNK, ERK1/2 and p38 MAP kinases increased significantly in 2 and 4 h Our results indicate a time-dependent decrease in Bcl-2 expression in response to HNE treatment. We observed a slight decrease in Bcl-X-L expression, while Mcl-1 amount remained unchanged Pro-apoptotic Bax and Bak expressions did not change; but truncated form of Bax disapperared Just after HNE treatment Our preliminary studies conducted by specific inhibitors of MAP kinase proteins indicate that phosphorylation of p38, JNK or ERK 1/2 proteins regulate the activation of Bcl-2 proteins, effecting the cellular outcome such as apoptosis