Iron-Induced Lipid-Peroxidation in Rat Liver Is Accompanied by Preferential Induction of Glutathione S-Transferase 8-8 Isozyme

M Khan, S. K. Srivastava, S. S. Singhal, M. Chaubey, S. Awasthi, D. R. Petersen, Ghulam Ansari, Y. C. Awasthi

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Abstract

Since previous studies from this laboratory have suggested that glutathione S-transferase (GST) 8-8 of rat belongs to a distinct subgroup of GST isozymes which may be involved in the detoxification of the products of lipid peroxidation (Zimniak et al., J. Biol. Chem.269, 992-1000, 1994), during the present studies we examined the effect of iron-induced lipid peroxidation on the expression of GST 8-8 in rat liver. Rats treated with 100 mg/kg body wt iron showed a significant increase in lipid peroxidation in liver. This was accompanied by a concomitant increase in the expression of GST 8-8 in liver as observed in isoelectrophoretic analysis of rat liver GSTs, and an increase in GST activity toward 4-HNE, a toxic product of lipid peroxidation toward which GST 8-8 displays high specific activity. Western blot studies using polyclonal antibodies specifically recognizing GST 8-8 also indicated that, among the GST isozymes of rat liver, GST 8-8 was preferentially induced upon iron treatment. These findings were further confirmed by purifying and quantitating GST 8-8 protein from the controls and iron-treated rats. Significant differences in the specific activities of GST 8-8 purified from the controls and iron-treated rats were observed, indicating that more than one GST isozyme related to GST 8-8 may be present in rat liver. This observation is consistent with the observed heterogeneity in mouse mGSTA4-4 which is an ortholog of rat GST 8-8. Iron treatment also caused significant increase in GSH levels probably because of de novo synthesis as indicated by an increase in γ-glutamyl cysteine synthetase activity. The results of these studies suggest that GST 8-8, and possibly other related GST isozymes, may play an important role in defense mechanisms against lipid peroxidation.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalToxicology and Applied Pharmacology
Volume131
Issue number1
DOIs
StatePublished - Mar 1995

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Glutathione Transferase
Liver
Lipid Peroxidation
Isoenzymes
Rats
Iron
Lipids
Detoxification
Poisons
Ligases
Cysteine

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Iron-Induced Lipid-Peroxidation in Rat Liver Is Accompanied by Preferential Induction of Glutathione S-Transferase 8-8 Isozyme. / Khan, M; Srivastava, S. K.; Singhal, S. S.; Chaubey, M.; Awasthi, S.; Petersen, D. R.; Ansari, Ghulam; Awasthi, Y. C.

In: Toxicology and Applied Pharmacology, Vol. 131, No. 1, 03.1995, p. 63-72.

Research output: Contribution to journalArticle

Khan, M ; Srivastava, S. K. ; Singhal, S. S. ; Chaubey, M. ; Awasthi, S. ; Petersen, D. R. ; Ansari, Ghulam ; Awasthi, Y. C. / Iron-Induced Lipid-Peroxidation in Rat Liver Is Accompanied by Preferential Induction of Glutathione S-Transferase 8-8 Isozyme. In: Toxicology and Applied Pharmacology. 1995 ; Vol. 131, No. 1. pp. 63-72.
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