Over-expression of 70-kDa heat shock protein confers protection against monochloramine-induced gastric mucosal cell injury

The major heat shock protein, HSP70, is known to be involved in cytoprotection against environmental stresses mediated by their function as a “molecular chaperone”. Monochloramine (NH 2Cl) is a potent cytotoxic oxidant generated by neutrophil-derived hypochlorous acid and Helicobacter pylori urease-...

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Bibliographic Details
Published in:Life sciences (1973) 2006-06, Vol.79 (3), p.300-305
Main Authors: Oyake, Jinko, Otaka, Michiro, Matsuhashi, Tamotsu, Jin, Mario, Odashima, Masaru, Komatsu, Koga, Wada, Isao, Horikawa, Youhei, Ohba, Reina, Hatakeyama, Natsumi, Itoh, Hideaki, Watanabe, Sumio
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Cells, Cultured
Chloramines - toxicity
Cytoprotection - genetics
Gastric Mucosa - drug effects
Gastric Mucosa - metabolism
Gastric Mucosa - pathology
Helicobacter pylori
HSP70
HSP70 Heat-Shock Proteins - genetics
HSP70 Heat-Shock Proteins - metabolism
Humans
Monochloramine (NH 2CI)
Mucosal protection
Necrosis
Necrosis - chemically induced
Necrosis - metabolism
Necrosis - pathology
Rats
Transcriptional Activation
Transfection
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Summary:The major heat shock protein, HSP70, is known to be involved in cytoprotection against environmental stresses mediated by their function as a “molecular chaperone”. Monochloramine (NH 2Cl) is a potent cytotoxic oxidant generated by neutrophil-derived hypochlorous acid and Helicobacter pylori urease-induced ammonia. In this study, to evaluate the cytoprotective effect of HSP70 against NH 2Cl-induced gastric mucosal cell injury, rat gastric mucosal cells (RGM-1) were stably transfected with pBK-CMV containing the human HSP70 gene (7018-RGM-1) or pBK-CMV alone (pBK-CMV-12) as control cells. These cells were treated with various concentrations of NH 2Cl. Cell Viability was determined by MTT assay and the direct plasma membrane damage was analyzed by lactate dehydrogenase (LDH) release assay. Apoptosis was determined by DNA fragmentation analysis. NH 2Cl caused injury to pBK-CMV-12 cells in a concentration-dependent manner. NH 2Cl-induced gastric cell injury was significantly deminished in HSP70 over-expressing cell line (7018-RGM-1) both necrosis and apoptosis compared to the control cell line (pBK-CMV-12) transfected with CMV vector alone. These result suggest that overexpression of HSP70 plays an important role in protecting gastric cells against NH 2Cl-induced injury.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2006.01.013