Preferential over-expression of the class alpha rat Ya2 glutathione S-transferase subunit in livers bearing aflatoxin-induced pre-neoplastic nodules

Comparison of the primary structures of Ya1 and Ya2 with cloned class alpha glutathione S-transferase cDNA sequences

J D Hayes, L A Kerr, D J Harrison, A D Cronshaw, A G Ross, G E Neal

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    16 Citations (Scopus)

    Abstract

    Normal rat liver expresses Ya (Mr 25,500), Yc (Mr 27,500) and Yk (Mr 25,000) Class Alpha glutathione S-transferase (GST) subunits. The Ya-type subunit can be resolved into two separate polypeptides, designated Ya1 and Ya2, by reverse-phase h.p.l.c. In rat livers that possess aflatoxin B1-induced pre-neoplastic nodules, a marked increase is observed in the expression of Ya1, Ya2, Yc and Yk; of these subunits, Ya2 exhibited the greatest increase in concentration. The Ya1 and Ya2 subunits isolated from nodule-bearing livers were cleaved with CNBr, and the purified peptides were subjected to automated amino-acid-sequence analysis. Differences in the primary structures of the two Ya GST subunits were found at positions 31, 34, 107 and 117. These data demonstrate that Ya1 and Ya2 are distinct polypeptides and are the products of separate genes. The amino acid sequences obtained from Ya1 and Ya2 were compared with the cloned cDNAs pGTB 38 [Pickett, Telakowski-Hopkins, Ding, Argenbright & Lu (1984) J. Biol. Chem. 259, 4112-4115] and pGTR 261 [Lai, Li, Weiss, Reddy & Tu (1984) J. Biol. Chem. 259, 5182-5188], which encode rat Ya-type subunits. From these comparisons it appears probable that Ya1 represents the GST subunit encoded by pGTR 261, whereas Ya2 represents the subunit encoded by pGTB 38. It is likely that the over-expression of Ya1 and Ya2 in nodule-bearing livers is of major significance in the acquired resistance of nodules to aflatoxin B1, since previous work [Coles, Meyer, Ketterer, Stanton & Garner (1985) Carcinogenesis 6, 693-697] has shown that the Ya-type GST subunit has high activity towards aflatoxin B1 8,9-epoxide.

    Original languageEnglish
    Pages (from-to)295-302
    Number of pages8
    JournalBiochemical Journal
    Volume268
    Issue number2
    DOIs
    Publication statusPublished - 1 Jun 1990

    Fingerprint

    Bearings (structural)
    Aflatoxins
    Glutathione Transferase
    Liver
    Rats
    Complementary DNA
    Aflatoxin B1
    Peptides
    Amino Acids
    Protein Sequence Analysis
    Amino Acid Sequence
    Carcinogenesis
    Genes
    glutathione S-transferase alpha

    Keywords

    • Aflatoxins
    • Amino Acid Sequence
    • Animals
    • Biomarkers, Tumor
    • Carcinogens
    • Chromatography, High Pressure Liquid
    • Cyanogen Bromide
    • DNA/analysis
    • Drug Resistance
    • Gene Expression
    • Glutathione Transferase/biosynthesis
    • Liver/cytology
    • Liver Neoplasms/enzymology
    • Molecular Sequence Data
    • Peptides
    • Precancerous Conditions/chemically induced
    • Rats
    • Rats, Inbred F344
    • Recombinant Proteins/biosynthesis

    Cite this

    @article{7510e4dbcd654d6c989bf67977e76906,
    title = "Preferential over-expression of the class alpha rat Ya2 glutathione S-transferase subunit in livers bearing aflatoxin-induced pre-neoplastic nodules: Comparison of the primary structures of Ya1 and Ya2 with cloned class alpha glutathione S-transferase cDNA sequences",
    abstract = "Normal rat liver expresses Ya (Mr 25,500), Yc (Mr 27,500) and Yk (Mr 25,000) Class Alpha glutathione S-transferase (GST) subunits. The Ya-type subunit can be resolved into two separate polypeptides, designated Ya1 and Ya2, by reverse-phase h.p.l.c. In rat livers that possess aflatoxin B1-induced pre-neoplastic nodules, a marked increase is observed in the expression of Ya1, Ya2, Yc and Yk; of these subunits, Ya2 exhibited the greatest increase in concentration. The Ya1 and Ya2 subunits isolated from nodule-bearing livers were cleaved with CNBr, and the purified peptides were subjected to automated amino-acid-sequence analysis. Differences in the primary structures of the two Ya GST subunits were found at positions 31, 34, 107 and 117. These data demonstrate that Ya1 and Ya2 are distinct polypeptides and are the products of separate genes. The amino acid sequences obtained from Ya1 and Ya2 were compared with the cloned cDNAs pGTB 38 [Pickett, Telakowski-Hopkins, Ding, Argenbright & Lu (1984) J. Biol. Chem. 259, 4112-4115] and pGTR 261 [Lai, Li, Weiss, Reddy & Tu (1984) J. Biol. Chem. 259, 5182-5188], which encode rat Ya-type subunits. From these comparisons it appears probable that Ya1 represents the GST subunit encoded by pGTR 261, whereas Ya2 represents the subunit encoded by pGTB 38. It is likely that the over-expression of Ya1 and Ya2 in nodule-bearing livers is of major significance in the acquired resistance of nodules to aflatoxin B1, since previous work [Coles, Meyer, Ketterer, Stanton & Garner (1985) Carcinogenesis 6, 693-697] has shown that the Ya-type GST subunit has high activity towards aflatoxin B1 8,9-epoxide.",
    keywords = "Aflatoxins, Amino Acid Sequence, Animals, Biomarkers, Tumor, Carcinogens, Chromatography, High Pressure Liquid, Cyanogen Bromide, DNA/analysis, Drug Resistance, Gene Expression, Glutathione Transferase/biosynthesis, Liver/cytology, Liver Neoplasms/enzymology, Molecular Sequence Data, Peptides, Precancerous Conditions/chemically induced, Rats, Rats, Inbred F344, Recombinant Proteins/biosynthesis",
    author = "Hayes, {J D} and Kerr, {L A} and Harrison, {D J} and Cronshaw, {A D} and Ross, {A G} and Neal, {G E}",
    year = "1990",
    month = "6",
    day = "1",
    doi = "10.1042/bj2680295",
    language = "English",
    volume = "268",
    pages = "295--302",
    journal = "Biochemical Journal",
    issn = "0264-6021",
    publisher = "Portland Press",
    number = "2",

    }

    TY - JOUR

    T1 - Preferential over-expression of the class alpha rat Ya2 glutathione S-transferase subunit in livers bearing aflatoxin-induced pre-neoplastic nodules

    T2 - Comparison of the primary structures of Ya1 and Ya2 with cloned class alpha glutathione S-transferase cDNA sequences

    AU - Hayes, J D

    AU - Kerr, L A

    AU - Harrison, D J

    AU - Cronshaw, A D

    AU - Ross, A G

    AU - Neal, G E

    PY - 1990/6/1

    Y1 - 1990/6/1

    N2 - Normal rat liver expresses Ya (Mr 25,500), Yc (Mr 27,500) and Yk (Mr 25,000) Class Alpha glutathione S-transferase (GST) subunits. The Ya-type subunit can be resolved into two separate polypeptides, designated Ya1 and Ya2, by reverse-phase h.p.l.c. In rat livers that possess aflatoxin B1-induced pre-neoplastic nodules, a marked increase is observed in the expression of Ya1, Ya2, Yc and Yk; of these subunits, Ya2 exhibited the greatest increase in concentration. The Ya1 and Ya2 subunits isolated from nodule-bearing livers were cleaved with CNBr, and the purified peptides were subjected to automated amino-acid-sequence analysis. Differences in the primary structures of the two Ya GST subunits were found at positions 31, 34, 107 and 117. These data demonstrate that Ya1 and Ya2 are distinct polypeptides and are the products of separate genes. The amino acid sequences obtained from Ya1 and Ya2 were compared with the cloned cDNAs pGTB 38 [Pickett, Telakowski-Hopkins, Ding, Argenbright & Lu (1984) J. Biol. Chem. 259, 4112-4115] and pGTR 261 [Lai, Li, Weiss, Reddy & Tu (1984) J. Biol. Chem. 259, 5182-5188], which encode rat Ya-type subunits. From these comparisons it appears probable that Ya1 represents the GST subunit encoded by pGTR 261, whereas Ya2 represents the subunit encoded by pGTB 38. It is likely that the over-expression of Ya1 and Ya2 in nodule-bearing livers is of major significance in the acquired resistance of nodules to aflatoxin B1, since previous work [Coles, Meyer, Ketterer, Stanton & Garner (1985) Carcinogenesis 6, 693-697] has shown that the Ya-type GST subunit has high activity towards aflatoxin B1 8,9-epoxide.

    AB - Normal rat liver expresses Ya (Mr 25,500), Yc (Mr 27,500) and Yk (Mr 25,000) Class Alpha glutathione S-transferase (GST) subunits. The Ya-type subunit can be resolved into two separate polypeptides, designated Ya1 and Ya2, by reverse-phase h.p.l.c. In rat livers that possess aflatoxin B1-induced pre-neoplastic nodules, a marked increase is observed in the expression of Ya1, Ya2, Yc and Yk; of these subunits, Ya2 exhibited the greatest increase in concentration. The Ya1 and Ya2 subunits isolated from nodule-bearing livers were cleaved with CNBr, and the purified peptides were subjected to automated amino-acid-sequence analysis. Differences in the primary structures of the two Ya GST subunits were found at positions 31, 34, 107 and 117. These data demonstrate that Ya1 and Ya2 are distinct polypeptides and are the products of separate genes. The amino acid sequences obtained from Ya1 and Ya2 were compared with the cloned cDNAs pGTB 38 [Pickett, Telakowski-Hopkins, Ding, Argenbright & Lu (1984) J. Biol. Chem. 259, 4112-4115] and pGTR 261 [Lai, Li, Weiss, Reddy & Tu (1984) J. Biol. Chem. 259, 5182-5188], which encode rat Ya-type subunits. From these comparisons it appears probable that Ya1 represents the GST subunit encoded by pGTR 261, whereas Ya2 represents the subunit encoded by pGTB 38. It is likely that the over-expression of Ya1 and Ya2 in nodule-bearing livers is of major significance in the acquired resistance of nodules to aflatoxin B1, since previous work [Coles, Meyer, Ketterer, Stanton & Garner (1985) Carcinogenesis 6, 693-697] has shown that the Ya-type GST subunit has high activity towards aflatoxin B1 8,9-epoxide.

    KW - Aflatoxins

    KW - Amino Acid Sequence

    KW - Animals

    KW - Biomarkers, Tumor

    KW - Carcinogens

    KW - Chromatography, High Pressure Liquid

    KW - Cyanogen Bromide

    KW - DNA/analysis

    KW - Drug Resistance

    KW - Gene Expression

    KW - Glutathione Transferase/biosynthesis

    KW - Liver/cytology

    KW - Liver Neoplasms/enzymology

    KW - Molecular Sequence Data

    KW - Peptides

    KW - Precancerous Conditions/chemically induced

    KW - Rats

    KW - Rats, Inbred F344

    KW - Recombinant Proteins/biosynthesis

    U2 - 10.1042/bj2680295

    DO - 10.1042/bj2680295

    M3 - Article

    VL - 268

    SP - 295

    EP - 302

    JO - Biochemical Journal

    JF - Biochemical Journal

    SN - 0264-6021

    IS - 2

    ER -