Helicobacter pylori infection induces STAT3 phosphorylation on Ser727 and autophagy in human gastric epithelial cells and mouse stomach.

Autor: Piao JY; Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea., Kim SJ; Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea., Kim DH; Department of Chemistry, College of Convergence and Integrated Science, Kyonggi University, Suwon, Gyeonggi-do, 16227, South Korea., Park JH; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea., Park SA; Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan, 31538, South Korea., Han HJ; Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea., Na HK; Department of Food Science and Biotechnology, College of Knowledge-Based Services Engineering, Sungshin Women's University, Seoul, 01133, South Korea., Yoon K; Department of Internal Medicine and Digestive Disease Research Institute, Wonkwang University Sanbon Hospital, Gunpo, Gyeonggi-do, 15865, South Korea., Lee HN; Laboratory of Immunology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA., Kim N; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea., Hahm KB; Digestive Disease Center, CHA University Bundang Medical Center, Seongnam, Gyunggi-do, 13496, South Korea., Surh YJ; Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea. surh@snu.ac.kr.; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, South Korea. surh@snu.ac.kr.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Sep 24; Vol. 10 (1), pp. 15711. Date of Electronic Publication: 2020 Sep 24.
DOI: 10.1038/s41598-020-72594-3
Abstrakt: Helicobacter pylori (H. pylori) infection is considered as one of the principal risk factors of gastric cancer. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated gastric carcinogenesis. In the canonical STAT3 pathway, phosphorylation of STAT3 on Tyr705 is a major event of STAT3 activation. However, recent studies have demonstrated that STAT3 phosphorylated on Ser727 has an independent function in mitochondria. In the present study, we found that human gastric epithelial AGS cells infected with H. pylori resulted in localization of STAT3 phosphorylated on Ser727 (P-STAT3 Ser727 ), predominantly in the mitochondria. Notably, H. pylori-infected AGS cells exhibited the loss of mitochondrial integrity and increased expression of the microtubule-associated protein light chain 3 (LC3), the autophagosomal membrane-associated protein. Treatment of AGS cells with a mitophagy inducer, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), resulted in accumulation of P-STAT3 Ser727 in mitochondria. In addition, the elevated expression and mitochondrial localization of LC3 induced by H. pylori infection were attenuated in AGS cells harboring STAT3 mutation defective in Ser727 phosphorylation (S727A). We also observed that both P-STAT3 Ser727 expression and LC3 accumulation were increased in the mitochondria of H. pylori-inoculated mouse stomach.
Databáze: MEDLINE
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