Changes in glucose-6-phosphate dehydrogenase and malic enzyme gene expression in acute hepatic injury induced by thioacetamide
NADPH-generating enzymes, glucose-6-phosphate dehydrogenase (G6PDH), and malic enzyme (ME) were studied in rat liver when necrosis and regeneration were induced by a single sublethal dose of thioacetamide (6.6 mmol/kg). Both enzyme activities decreased sharply at 12–24 hr of treatment and increased...
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Published in | Biochemical pharmacology Vol. 51; no. 9; pp. 1159 - 1163 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
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New York, NY
Elsevier Inc
03.05.1996
Elsevier Science |
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Abstract | NADPH-generating enzymes, glucose-6-phosphate dehydrogenase (G6PDH), and malic enzyme (ME) were studied in rat liver when necrosis and regeneration were induced by a single sublethal dose of thioacetamide (6.6 mmol/kg). Both enzyme activities decreased sharply at 12–24 hr of treatment and increased thereafter. These biphasic changes are related to the sequential processes of liver injury and hepatocellular regeneration. Expression of mRNA for G6PDH decreased at 12 hr following thioacetamide injection and increased during liver regeneration, reaching its highest levels of expression at 48 hr (247% of the control), parallel to the peak of DNA synthesis. Expression of ME decreased at 12–24 hr and increased during the postnecrotic regenerating process, reaching only half of the control value at 96 hr. A relationship between mRNA G6PDH gene expression, oxidative stress (detected by the GSH/GSSG ratio and malondialdehyde (MDA) concentration), and DNA synthesis is proposed. |
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AbstractList | NADPH-generating enzymes, glucose-6-phosphate dehydrogenase (G6PDH), and malic enzyme (ME) were studied in rat liver when necrosis and regeneration were induced by a single sublethal dose of thioacetamide (6.6 mmol/kg). Both enzyme activities decreased sharply at 12-24 hr of treatment and increased thereafter. These biphasic changes are related to the sequential processes of liver injury and hepatocellular regeneration. Expression of mRNA for G6PDH decreased at 12 hr following thioacetamide injection and increased during liver regeneration, reaching its highest levels of expression at 48 hr (247% of the control), parallel to the peak of DNA synthesis. Expression of ME decreased at 12-24 hr and increased during the postnecrotic regenerating process, reaching only half of the control value at 96 hr. A relationship between mRNA G6PDH gene expression, oxidative stress (detected by the GSH/GSSG ratio and malondialdehyde (MDA) concentration), and DNA synthesis is proposed. |
Author | Cascales, María Díez-Fernández, Carmen Sanz, Nuria |
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Keywords | NADPH-generating enzymes necrosis regeneration G6PDH ME MDA gene expression oxidative stress Oxidative stress Glucose-6-phosphate 1-dehydrogenase Rat Enzyme Liver Rodentia Hepatic disease ) Gene expression Mechanism Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP Necrosis Regeneration Vertebrata Experimental disease Mammalia Digestive diseases Oxidoreductases |
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Chronology of perturbations and metabolic significance publication-title: Mol Pharmacol contributor: fullname: Cerdán – volume: 210 start-page: 26 year: 1994 ident: 10.1016/0006-2952(96)00030-5_BIB8 article-title: Glucose-6-phosphate dehydrogenase gene expression in fetal hepatocyte primary cultures under non-proliferative and proliferative conditions publication-title: Exp Cell Res doi: 10.1006/excr.1994.1004 contributor: fullname: Molero – volume: 162 start-page: 156 year: 1987 ident: 10.1016/0006-2952(96)00030-5_BIB18 article-title: Single-step method of RNA isolation by acid guanidinium thyocyanate-phenol-chloroform extraction publication-title: Anal Biochem contributor: fullname: Chhomezynski – volume: 12 start-page: 233 year: 1991 ident: 10.1016/0006-2952(96)00030-5_BIB5 article-title: Alterations in hepatic peroxidation mechanisms in thioacetamide-induced tumors in rats publication-title: Carcinogenesis doi: 10.1093/carcin/12.2.233 contributor: fullname: Cascales – volume: 13 start-page: 120 year: 1993 ident: 10.1016/0006-2952(96)00030-5_BIB6 article-title: Induction of G6PDH in rat hepatocytes under oxidative stress conditions publication-title: Toxicologist contributor: fullname: Cramer – volume: 168 start-page: 487 year: 1987 ident: 10.1016/0006-2952(96)00030-5_BIB3 article-title: Influence of diet on the transcriptional and post-transcriptional regulation of malic enzyme induction in rat liver publication-title: J Biol Chem doi: 10.1111/j.1432-1033.1987.tb13443.x contributor: fullname: Karsurada – volume: 162 start-page: 156 year: 1976 ident: 10.1016/0006-2952(96)00030-5_BIB16 article-title: A fluorimetric method for determination of oxidized and reduced glutathione in tissues publication-title: Anal Biochem contributor: fullname: Hissin – volume: 8 start-page: 174 year: 1994 ident: 10.1016/0006-2952(96)00030-5_BIB4 article-title: Glucose-6-phosphate dehydrogenase: a “housekeeping” enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress publication-title: FASEB J doi: 10.1096/fasebj.8.2.8119488 contributor: fullname: Kletzien – volume: 205 start-page: 433 year: 1992 ident: 10.1016/0006-2952(96)00030-5_BIB2 article-title: Nutritional and hormonal regulation of lipogenicenzyme gene expression in rat liver publication-title: Eur J Biochem doi: 10.1111/j.1432-1033.1992.tb16797.x contributor: fullname: Iritani – start-page: 55 year: 1993 ident: 10.1016/0006-2952(96)00030-5_BIB20 article-title: Metabolic heterogeneity of the liver contributor: fullname: Katz |
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SubjectTerms | Animals Biological and medical sciences Fundamental and applied biological sciences. Psychology gene expression Gene Expression Regulation, Enzymologic - drug effects Glucosephosphate Dehydrogenase - genetics Liver - drug effects Liver - injuries Liver. Bile. Biliary tracts Malate Dehydrogenase - genetics Male NADPH-generating enzymes necrosis Oxidative Stress Rats Rats, Wistar regeneration RNA, Messenger - genetics RNA, Messenger - metabolism Thioacetamide - toxicity Vertebrates: digestive system |
Title | Changes in glucose-6-phosphate dehydrogenase and malic enzyme gene expression in acute hepatic injury induced by thioacetamide |
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