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Experimental Biology and Medicine 228:1089-1095 (2003)
© 2003 Society for Experimental Biology and Medicine

ORIGINAL RESEARCH ARTICLE

Molecular Mechanism of Adaptive Cytoprotection Induced by Ethanol in Human Gastric Cells

Shinji Tsutsumi, Shinji Mima, Wataru Tomisato, Tatsuya Hoshino, Tomofusa Tsuchiya and Tohru Mizushima1

Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan

Adaptive cytoprotection is the process by which the pretreatment of cells with low concentrations of a noxious agent prevents the damage caused by a subsequent exposure of those cells to higher concentrations of that same agent. In this study, a human gastric carcinoma cell line was used to examine the molecular mechanism of adaptive cytoprotection induced by ethanol. Pretreatment of cells with 1%–4% ethanol made cells resistant to a subsequent exposure to 8% ethanol. This adaptive cytoprotection was accompanied by an increase in prostaglandin E2 synthesis and was partially inhibited by inhibitors of cyclooxygenase-2, but not by an inhibitor of cyclooxygenase-1. Furthermore, the adaptive cytoprotection was not dependent on newly synthesized proteins and was inhibited by a protein tyrosine kinase inhibitor. Based on these results, it is proposed that the stimulation of cyclooxygenase-2-dependent prostaglandin E2 synthesis, which is regulated post-translationally by protein tyrosine phosphorylation, plays an important role in adaptive cytoprotection induced by ethanol in gastric cells.

Key Words: prostaglandin E2 • protein tyrosine phosphorylation • post-translational regulation




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M. Aburaya, K.-I. Tanaka, T. Hoshino, S. Tsutsumi, K. Suzuki, M. Makise, R. Akagi, and T. Mizushima
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J. Biol. Chem., November 3, 2006; 281(44): 33422 - 33432.
[Abstract] [Full Text] [PDF]


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