Molecular mechanism of adaptive cytoprotection induced by ethanol in human gastric cells.
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.
Tsutsumi
Shinji
S
Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
Mima
Shinji
S
Tomisato
Wataru
W
Hoshino
Tatsuya
T
Tsuchiya
Tomofusa
T
Mizushima
Tohru
T
D045744:Cell Line, Tumor; D003470:Culture Media / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019610:Cytoprotection; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013270:Stomach / Q000166:cytology*; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D003470:Culture Media; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D000431:Ethanol; D014443:Tyrosine; D019833:Genistein; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin