Elevations of hepatic quinone reductase, glutathione, and α- and μ- class glutathione S-transferase isoforms in mice with chronic hepatitis: A compensatory response to injury Journal Article
| Authors: | Fernandes, C. L.; Dong, J. H.; Roebuck, B. D.; Chisari, F. V.; Montali, J. A.; Schmidt, D. E. Jr; Prochaska, H. J. |
| Article Title: | Elevations of hepatic quinone reductase, glutathione, and α- and μ- class glutathione S-transferase isoforms in mice with chronic hepatitis: A compensatory response to injury |
| Abstract: | Hepatic levels of GSH and Phase II detoxication enzymes were compared to biochemical and histological indices of hepatic damage in 4- to 76-week-old nontransgenic mice and their transgenic littermates that overexpress the hepatitis B virus large envelope protein. The mice were fed a low-sucrose AIN-76A diet ad libitum. Hepatic-specific activities of quinone reductase (QR) and glutathione S-transferase (GST) were increased 2- to 10-fold beginning at 12 weeks of age in transgenic mice and correlated with increases in serum alanine aminotransferase (ALT) (r = 0.84 and 0.59, respectively). Quantitative histological analysis demonstrated that apoptosis was the predominant feature in 4- to 12-week-old transgenic mice, whereas necrosis and inflammation predominated at later time points. Surprisingly, 3-fold elevations in ALT were observed beginning at 52 weeks of age in nontransgenic mice, and hepatic-specific activities of QR and GST were also modestly increased in elderly nontransgenic animals. In contrast to transgenic mice, apoptosis was not a prominent feature. The strongest histological correlates to ALT in 4- to 76-week-old nontransgenic mice were necrosis and inflammation (r > 0.96), which in turn may have been evoked by hepatic fat accumulation. Profiles of specific GST isoforms were quantitated chromatographically and identified by sequencing tryptic digests. The Ya1 subunit of α-class GST was markedly increased from undetectable levels in transgenic mice, while more modest increases were observed in nontransgenic mice more than 1 year old. Fivefold elevations of the Yb1 subunit, a constitutively expressed μ- class GST, were found in transgenic mice older than 4 weeks of age, while 2- fold increases were observed in nontransgenic animals that were more than 1 year old. These studies demonstrate that selected increases in Phase II detoxication enzymes are a stereotyped response to chronic hepatitis that is strikingly reminiscent of the treatment of mice with anticarcinogenic enzyme inducers. |
| Keywords: | controlled study; nonhuman; mouse; animal tissue; apoptosis; animal experiment; animal model; inflammation; enzyme activity; age; transgenic mouse; dna strand breakage; alanine aminotransferase; liver; enzyme regulation; glutathione transferase; oxidative stress; detoxification; drug metabolism; liver enzyme; hepatitis b virus; enzyme subunit; glutathione; carcinogen; chemoprevention; liver necrosis; reduced nicotinamide adenine dinucleotide (phosphate) dehydrogenase (quinone); chronic hepatitis; malonaldehyde; cancer; male; priority journal; article; hepatitis b surface antigen |
| Journal Title: | Archives of Biochemistry and Biophysics |
| Volume: | 331 |
| Issue: | 1 |
| ISSN: | 0003-9861 |
| Publisher: | Elsevier Inc. |
| Date Published: | 1996-07-01 |
| Start Page: | 104 |
| End Page: | 116 |
| Language: | English |
| DOI: | 10.1006/abbi.1996.0288 |
| PUBMED: | 8660689 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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