Restoration of heat shock protein70 suppresses gastric mucosal inducible nitric oxide synthase expression induced by Helicobacter pylori.
Heat shock proteins (HSPs) are crucial for the maintenance of cell integrity during normal cellular growth as well as during pathophysiological conditions. While functioning mainly as molecular chaperones, HSPs also appear to be involved in diverse biological activities, such as apoptosis, carcinogenesis, and cytoprotection from cytotoxic damage. Infection with Helicobacter pylori causes inflammation in the gastric mucosa, leading to gastritis, gastric ulcers, duodenal ulcer disease, and even gastric cancer, but the role of HSPs in H. pylori-associated gastropathy is not known. Using two-dimensional electrophoretic analysis, we have observed significant shifts in HSP profiles after H. pylori infection in RGM-1 cells. We therefore evaluated the effect of treatments that induce HSPs on H. pylori-induced inducible nitric oxide synthase (iNOS) expression. We found that H. pylori infection significantly attenuated the expression of HSP70, whereas exposure of cells to noncytotoxic heat shock or geranylgeranylacetone restored HSP70 expression, as well as suppressing the expression of iNOS, a major cause of H. pylori-induced gastric tissue damage. Our results suggest that induction of HSP70 confers cytoprotection against H. pylori infection by inhibiting the expression of iNOS. In conclusion, these results provide important insights into the flux in HSPs profiles in response to H. pylori infection and highlight the cytoprotective role of HSP70 in H. pylori infection.
Yeo
Marie
M
Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
Park
Hyun-kyung
HK
Kim
Dong-Kyu
DK
Cho
Sung Won
SW
Kim
Young Suk
YS
Cho
Sang Yun
SY
Paik
Young-ki
YK
Hahm
Ki-Baik
KB
D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D005753:Gastric Mucosa / Q000201:enzymology / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats
D018840:HSP70 Heat-Shock Proteins; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat