Alterations in inositol phosphate production during oxidative stress in isolated hepatocytes.
The level of inositol phosphates was measured in rat hepatocytes treated with 2-methyl-1,4-naphthoquinone (menadione) or tert-butyl hydroperoxide, which cause Ca2+ mobilization from intracellular stores and an increase in cytosolic free Ca2+ concentration. Although neither agent produced any apparent changes in the resting level of inositol phosphates, pretreatment of hepatocytes with either menadione or tert-butyl hydroperoxide, as well as with several sulfhydryl reagents, markedly inhibited the increase in inositol phosphates induced by both hormonal and nonhormonal stimuli. Addition of dithiothreitol to menadione- or tert-butyl hydroperoxide-treated hepatocytes reversed this inhibition and reestablished responsiveness to extracellular stimuli. Our findings suggest that the inhibition of the inositol phosphate response by menadione and tert-butyl hydroperoxide occurs through the modification of critical sulfhydryl group(s) and that the alterations in intracellular Ca2+ homeostasis occurring during the metabolism of menadione and tert-butyl hydroperoxide in hepatocytes are not mediated by inositol phosphates.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000535:Aluminum / Q000494:pharmacology; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology; D013403:Sugar Phosphates / Q000096:biosynthesis*; D014812:Vitamin K / Q000494:pharmacology
D017607:Aluminum Compounds; D002712:Chlorides; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D000804:Angiotensin II; D014812:Vitamin K; D000077410:Aluminum Chloride; D000255:Adenosine Triphosphate; D012969:Sodium Fluoride; D000535:Aluminum; D003676:Deferoxamine; D002118:Calcium; D004229:Dithiothreitol; D004837:Epinephrine