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- Title
The secreted antigen, HP0175, of H elicobacter pylori links the unfolded protein response ( UPR) to autophagy in gastric epithelial cells.
- Authors
Halder, Priyanka; Datta, Chandreyee; Kumar, Ranjeet; Sharma, Arun Kumar; Basu, Joyoti; Kundu, Manikuntala
- Abstract
Autophagy is an intracellular catabolic process that is required to maintain cellular homeostasis. Pathogen-elicited host cell autophagy may favour containment of infection or may help in bacterial survival. Pathogens have developed the ability to modulate host autophagy. The secreted antigen HP0175, a peptidyl prolyl cis,trans isomerase of H elicobacter pylori, has moonlighting functions with reference to host cells. Here we show that it executes autophagy in gastric epithelial cells. Autophagy is dependent on the unfolded protein response ( UPR) that activates the expression of PKR-like ER kinase ( PERK). This is accompanied by phosphorylation of eukaryotic initiation factor 2α ( eIF-2α) and transcriptional activation of ATF4 and CHOP. Knockdown of UPR-related genes inhibits the conversion of LC3 I to LC3 II, a marker of autophagy. The autophagy-inducing ability of H . pylori is compromised when cells are infected with an isogenic hp0175 mutant. Autophagy precedes apoptosis. Silencing of BECLIN 1 augments cleavage of caspase 3 as well as apoptosis. Increased apoptosis of gastric epithelial cells is known to be linked to H . pylori-mediated gastric inflammation and carcinogenesis. To the best of our knowledge, this study provides the first demonstration of how HP0175 endowed with moonlighting functions links UPR-dependent autophagy and apoptosis during H . pylori infection.
- Subjects
SECRETION; ANTIGENS; AUTOPHAGY; EPITHELIAL cells; HELICOBACTER pylori; DENATURATION of proteins
- Publication
Cellular Microbiology, 2015, Vol 17, Issue 5, p714
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/cmi.12396