AMP-activated protein kinase activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis

• H Pylori activates AMPK in transformed and primary gastric epithelial cells (GECs).
• AMPK inhibitor compound C increases apoptosis by H Pylori in GECs.
• AMPK knockdown by targeted shRNAs promotes apoptosis in H pylori-infected GECs.
• AMPK activators, or AMPKα1 over-expression, inhibits H Pylori-induced GEC apoptosis.
• TAK1 potentially serves as upstream kinase to mediate AMPK activation by H pylori.

Helicobacter pylori (H pylori), infecting half of the world’s population, causes gastritis, duodenal and gastric ulcer, and gastric cancers. AMP-activated protein kinase (AMPK) is a highly conserved regulator of cellular energy and metabolism. Recent studies indicated an important role for AMPK in promoting cell survival. In this study, we discovered that H Pylori induced AMPK activation in transformed (GEC-1 line) and primary human gastric epithelial cells (GECs). Inhibition of H Pylori-stimulated AMPK kinase activity by AMPK inhibitor compound C exacerbated apoptosis in transformed and primary GECs. Meanwhile, downregulation of AMPK expression by targeted shRNAs promoted apoptosis in H pylori-infected GECs. In contrast, A-769662 and resveratrol, two known AMPK activators, or AMPKα1 over-expression, enhanced H Pylori-induced AMPK activation, and inhibited GEC apoptosis. Our data suggested that transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) could be the upstream kinase for AMPK activation by H pylori. Partial depletion of TAK1 by shRNAs not only inhibited AMPK activation, but also suppressed survival of H pylori-infected GECs. Taken together, these results suggest that TAK1-dependent AMPK activation protects GECs from H pylori-Induced apoptosis.