Cloning of cDNAs from fetal rat liver encoding glutathione S-transferase Yc polypeptides. The Yc2 subunit is expressed in adult rat liver resistant to the hepatocarcinogen aflatoxin B1

John D. Hayes (Lead / Corresponding author), Truyen Nguyen, David J. Judah, David G. Petersson, Gordon E. Neal

    Research output: Contribution to journalArticle

    72 Citations (Scopus)

    Abstract

    Fetal rat liver possesses substantial levels of glutathione S-transferase (GST) activity toward aflatoxin B1-8,9-epoxide. The enzyme responsible for this activity is an Alpha-class GST heterodimer comprising Yc1 and Yc2 subunits. The cDNAs encoding these polypeptides have been cloned and shown to share approximately 91% identity over 920 base pairs, extending from nucleotide -23 to the AATAAA polyadenylation signal. GST Yc2Yc2 expressed in Escherichia coli was found to exhibit 150-fold greater activity toward aflatoxin B1-8,9-epoxide than GST Yc1Yc1. Comparison between the structures of Alpha-class GST suggests that tyrosine at residue 108 and/or aspartate at residue 208 is responsible for the high aflatoxin B1 detoxication capacity of Yc2. Immunoblotting and enzyme assays have shown that liver from adult female rats contains about 10-fold greater levels of Yc2 than is found in liver from adult male rats. This sex-specific expression of Yc2 in adult rat liver may contribute to the relative insensitivity of female rats to aflatoxin B1. Dietary administration of oltipraz, a synthetic antioxidant which protects against aflatoxin-hepatocarcinogenesis, serves as an inducer of GST Yc2.

    Original languageEnglish
    Pages (from-to)20707-17
    Number of pages11
    JournalJournal of Biological Chemistry
    Volume269
    Issue number32
    Publication statusPublished - 12 Aug 1994

    Fingerprint

    Aflatoxin B1
    Cloning
    Glutathione Transferase
    Liver
    Rats
    Organism Cloning
    Complementary DNA
    Peptides
    Polyadenylation
    Aflatoxins
    Enzyme Assays
    Immunoblotting
    Aspartic Acid
    Base Pairing
    Tyrosine
    Enzymes
    Nucleotides
    Escherichia coli
    Antioxidants
    glutathione S-transferase Yc

    Keywords

    • Aflatoxin B1/analogs & derivatives
    • Amino Acid Sequence
    • Animals
    • Base Sequence
    • Carcinogens/toxicity
    • Cloning, Molecular
    • DNA, Complementary
    • Drug Resistance
    • Enzyme Induction
    • Escherichia coli/genetics
    • Female
    • Glutathione Transferase/chemistry
    • Humans
    • Inactivation, Metabolic
    • Liver/embryology
    • Male
    • Molecular Sequence Data
    • Peptide Fragments/genetics
    • Rats
    • Rats, Inbred F344
    • Sequence Homology, Amino Acid

    Cite this

    @article{e88a7debad2b4fdf859050f100ae4978,
    title = "Cloning of cDNAs from fetal rat liver encoding glutathione S-transferase Yc polypeptides. The Yc2 subunit is expressed in adult rat liver resistant to the hepatocarcinogen aflatoxin B1",
    abstract = "Fetal rat liver possesses substantial levels of glutathione S-transferase (GST) activity toward aflatoxin B1-8,9-epoxide. The enzyme responsible for this activity is an Alpha-class GST heterodimer comprising Yc1 and Yc2 subunits. The cDNAs encoding these polypeptides have been cloned and shown to share approximately 91{\%} identity over 920 base pairs, extending from nucleotide -23 to the AATAAA polyadenylation signal. GST Yc2Yc2 expressed in Escherichia coli was found to exhibit 150-fold greater activity toward aflatoxin B1-8,9-epoxide than GST Yc1Yc1. Comparison between the structures of Alpha-class GST suggests that tyrosine at residue 108 and/or aspartate at residue 208 is responsible for the high aflatoxin B1 detoxication capacity of Yc2. Immunoblotting and enzyme assays have shown that liver from adult female rats contains about 10-fold greater levels of Yc2 than is found in liver from adult male rats. This sex-specific expression of Yc2 in adult rat liver may contribute to the relative insensitivity of female rats to aflatoxin B1. Dietary administration of oltipraz, a synthetic antioxidant which protects against aflatoxin-hepatocarcinogenesis, serves as an inducer of GST Yc2.",
    keywords = "Aflatoxin B1/analogs & derivatives, Amino Acid Sequence, Animals, Base Sequence, Carcinogens/toxicity, Cloning, Molecular, DNA, Complementary, Drug Resistance, Enzyme Induction, Escherichia coli/genetics, Female, Glutathione Transferase/chemistry, Humans, Inactivation, Metabolic, Liver/embryology, Male, Molecular Sequence Data, Peptide Fragments/genetics, Rats, Rats, Inbred F344, Sequence Homology, Amino Acid",
    author = "Hayes, {John D.} and Truyen Nguyen and Judah, {David J.} and Petersson, {David G.} and Neal, {Gordon E.}",
    year = "1994",
    month = "8",
    day = "12",
    language = "English",
    volume = "269",
    pages = "20707--17",
    journal = "Journal of Biological Chemistry",
    issn = "0021-9258",
    publisher = "American Society for Biochemistry and Molecular Biology",
    number = "32",

    }

    Cloning of cDNAs from fetal rat liver encoding glutathione S-transferase Yc polypeptides. The Yc2 subunit is expressed in adult rat liver resistant to the hepatocarcinogen aflatoxin B1. / Hayes, John D. (Lead / Corresponding author); Nguyen, Truyen; Judah, David J.; Petersson, David G.; Neal, Gordon E.

    In: Journal of Biological Chemistry, Vol. 269, No. 32, 12.08.1994, p. 20707-17.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Cloning of cDNAs from fetal rat liver encoding glutathione S-transferase Yc polypeptides. The Yc2 subunit is expressed in adult rat liver resistant to the hepatocarcinogen aflatoxin B1

    AU - Hayes, John D.

    AU - Nguyen, Truyen

    AU - Judah, David J.

    AU - Petersson, David G.

    AU - Neal, Gordon E.

    PY - 1994/8/12

    Y1 - 1994/8/12

    N2 - Fetal rat liver possesses substantial levels of glutathione S-transferase (GST) activity toward aflatoxin B1-8,9-epoxide. The enzyme responsible for this activity is an Alpha-class GST heterodimer comprising Yc1 and Yc2 subunits. The cDNAs encoding these polypeptides have been cloned and shown to share approximately 91% identity over 920 base pairs, extending from nucleotide -23 to the AATAAA polyadenylation signal. GST Yc2Yc2 expressed in Escherichia coli was found to exhibit 150-fold greater activity toward aflatoxin B1-8,9-epoxide than GST Yc1Yc1. Comparison between the structures of Alpha-class GST suggests that tyrosine at residue 108 and/or aspartate at residue 208 is responsible for the high aflatoxin B1 detoxication capacity of Yc2. Immunoblotting and enzyme assays have shown that liver from adult female rats contains about 10-fold greater levels of Yc2 than is found in liver from adult male rats. This sex-specific expression of Yc2 in adult rat liver may contribute to the relative insensitivity of female rats to aflatoxin B1. Dietary administration of oltipraz, a synthetic antioxidant which protects against aflatoxin-hepatocarcinogenesis, serves as an inducer of GST Yc2.

    AB - Fetal rat liver possesses substantial levels of glutathione S-transferase (GST) activity toward aflatoxin B1-8,9-epoxide. The enzyme responsible for this activity is an Alpha-class GST heterodimer comprising Yc1 and Yc2 subunits. The cDNAs encoding these polypeptides have been cloned and shown to share approximately 91% identity over 920 base pairs, extending from nucleotide -23 to the AATAAA polyadenylation signal. GST Yc2Yc2 expressed in Escherichia coli was found to exhibit 150-fold greater activity toward aflatoxin B1-8,9-epoxide than GST Yc1Yc1. Comparison between the structures of Alpha-class GST suggests that tyrosine at residue 108 and/or aspartate at residue 208 is responsible for the high aflatoxin B1 detoxication capacity of Yc2. Immunoblotting and enzyme assays have shown that liver from adult female rats contains about 10-fold greater levels of Yc2 than is found in liver from adult male rats. This sex-specific expression of Yc2 in adult rat liver may contribute to the relative insensitivity of female rats to aflatoxin B1. Dietary administration of oltipraz, a synthetic antioxidant which protects against aflatoxin-hepatocarcinogenesis, serves as an inducer of GST Yc2.

    KW - Aflatoxin B1/analogs & derivatives

    KW - Amino Acid Sequence

    KW - Animals

    KW - Base Sequence

    KW - Carcinogens/toxicity

    KW - Cloning, Molecular

    KW - DNA, Complementary

    KW - Drug Resistance

    KW - Enzyme Induction

    KW - Escherichia coli/genetics

    KW - Female

    KW - Glutathione Transferase/chemistry

    KW - Humans

    KW - Inactivation, Metabolic

    KW - Liver/embryology

    KW - Male

    KW - Molecular Sequence Data

    KW - Peptide Fragments/genetics

    KW - Rats

    KW - Rats, Inbred F344

    KW - Sequence Homology, Amino Acid

    M3 - Article

    VL - 269

    SP - 20707

    EP - 20717

    JO - Journal of Biological Chemistry

    JF - Journal of Biological Chemistry

    SN - 0021-9258

    IS - 32

    ER -