AMP-activated protein kinase-α is involved in the autophagy and apoptosis caused by troglitazone

Abstract:

Abstract:［Objective］To reveal the mechanism of AMPK signaling in the autophagy and apoptosis caused by troglitazone (TZ)．［Methods］To investigate the effect of TZ on alteration of autophagy and apoptosis in HeLa cells，fluorescence microscopy，electron microscopy，western-blotting，siRNA interference，flow cytometry and MTS assay were used．［Results］TZ attenuated AMP-activated protein kinase-α (AMPKα) phosphorylation，and stimulates autophagic process in HeLa cells．TZ induced the accumulation of microtubule-associated protein 1 light chain 3-II (LC3-II)，and degradation of sequestosome 1 (SQSTM1/p62)，two markers of autophagy，occurring prior to the caspase activation．Compound C，an AMPK inhibitor，increased basal and inhibits TZ-stimulated LC3-II content and TZ-depended PARP cleavage． Knockdown of the gene encoding autophagic proteins and AMPK conferred the cells resistance to apoptosis by TZ．［Conclusion］ Taken together，these data demonstrate that AMPK is involved in TZ promote autophagy，which precedes and contributes to caspase-dependent apoptosis．