Abstract:
:Metabolism of tert-butyl hydroperoxide (TBHP, 2.0 mM) by glutathione peroxidase within isolated rat hepatocytes caused a rapid oxidation of intracellular reduced glutathione and ultimately NADPH through glutathione reductase. TBHP also caused the formation of surface blebs in the hepatocyte plasma membrane followed by the leakage of cytosolic enzymes, such as lactate dehydrogenase, into the incubation medium. Catechol (0.1 mM) protected hepatocytes from the cytotoxic effects of TBHP but did not prevent the rapid oxidation of glutathione indicating normal metabolism of TBHP through glutathione reductase. In contrast, addition of catechol to the hepatocyte incubations prevented TBHP-induced depletion of intracellular NADPH and increased the total NADP+ + NADPH concentration without altering significantly the intracellular NADP+ content or the NADPH/NADP + NADPH ratio. Catechol did not alter TBHP stimulation of the pentose phosphate pathway. Hepatocytes incubated with sublethal concentrations of TBHP (1.0 mM) did not leak lactate dehydrogenase into the medium but did lose intracellular potassium. In these experiments, TBHP caused a sustained increase in phosphorylase alpha activity suggesting that TBHP metabolism may be associated with a sustained increase in cytosolic free Ca2+. In the presence of catechol, phosphorylase alpha activity was increased by 5 min but returned toward control by 20 min. These data suggest that catechol may be protecting hepatocytes from TBHP-induced injury by preventing a sustained rise in cytosolic free Ca2+ concentration.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Rush GF,Yodis LA,Alberts Ddoi
10.1016/0041-008x(86)90267-xsubject
Has Abstractpub_date
1986-07-01 00:00:00pages
607-16issue
3eissn
0041-008Xissn
1096-0333journal_volume
84pub_type
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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journal_title:Toxicology and applied pharmacology
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更新日期:2019-06-15 00:00:00
abstract::The mechanism of action of Cd on Na,K-ATPase was investigated in two "classical" model systems, the shark rectal gland and rabbit kidney outer medulla. In lyophilized plasma membranes from dogfish rectal gland Cd inhibited Na,K-ATPase activity after 30 min of preincubation with an I50 of 1.3 x 10(-5) M. K-Dependent p-...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
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