Changes in the hepatic glutathione peroxidase redox system produced by coplanar polychlorinated biphenyls in Ah-responsive and -less-responsive strains of mice: Mechanism and implications for toxicity

Miho Hori, Hiroshi Kondo, Noritaka Ariyoshi, Hideyuki Yamada, Akira Hiratsuka, Tadashi Watabe, Kazuta Oguri

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The alteration in hepatic glutathione peroxidase (GPx) produced by polychlorinated biphenyls (PCBs) was studied in vivo in aryl hydrocarbon (Ah)-responsive C57BL and -less-responsive DBA strains of mice. 3,3',4,4',5-Pentachlorobiphenyl (PCB 126), one of the high-affinity ligands for the Ah receptor, significantly reduced Se-dependent GPx activity in C57BL mice, but not in DBA mice. A reduction in activity in C57BL mice was also observed following treatment with a high dose of 3,3',4,3'-tetrachlorobiphenyl with lesser affinity for the Ah receptor than PCB 126, but not by 2,2',5,5'-tetrachlorobiphenyl, a low-affinity ligand. To assess the effects on GPx in the liver, the content of reduced glutathione (GSH), an obligate co-factor for GPx, and the activity of two enzymes, γ-glutamyl transpeptidase (γ-GTP) and glutathione reductase (GR), which play a role in supplying GSH were determined after PCB treatment. The results showed that although the hepatic activity of γ-GTP and GR was affected differently by PCB 126, the content of GSH was slightly increased rather than reduced in both strains of mice. The activity of non-Se-dependent GPx, which is due to the catalysis by some isozymes of glutathione S-transferase (GST), was significantly increased only in C57BL mice by PCB 126 treatment. Immunoblot analysis demonstrated that the induction of the class θ GST, which is a potent reducer of peroxides (Hiratsuka et al., 1995. Biochem. Biophys. Res. Commun. 212, 743) reflects the enhancement of the above activity. These results suggest that (i) the PCB-induced reduction in Se-dependent GPx activity is mediated by a mechanism involving the Ah receptor; and (ii) a concomitant increase in the class θ GST partially rescues the Ah-responsive mice from coplanar PCB-induced oxidative stress.

Original languageEnglish
Pages (from-to)267-275
Number of pages9
JournalEnvironmental Toxicology and Pharmacology
Volume3
Issue number4
DOIs
Publication statusPublished - Sep 1 1997
Externally publishedYes

Keywords

  • 3,3',4,4',5-Pentachlorobiphenyl (PCB 126)
  • C57BL mice
  • DBA mice
  • Glutathione
  • Glutathione S-transferase
  • Non-Se-dependent glutathione peroxidase
  • Se-dependent glutathione peroxidase
  • γ-Glutamyl transpeptidase

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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