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
| Autor: | J D, Hayes, T, Nguyen, D J, Judah, D G, Petersson, G E, Neal |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Aflatoxin B1 DNA Complementary Base Sequence Sequence Homology Amino Acid Molecular Sequence Data Drug Resistance Peptide Fragments Rats Inbred F344 Rats Liver Enzyme Induction Inactivation Metabolic Carcinogens Escherichia coli Animals Humans Female Amino Acid Sequence Cloning Molecular Glutathione Transferase |
| Zdroj: | The Journal of biological chemistry. 269(32) |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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