STRUCTURE AND REGULATION OF ETHANOL-INDUCIBLE CYTOCHROME P450 GENE

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The microsomal enzyme induced by feeding of alcohol is also the same enzyme responsible for the elevation of serum 1,2- propanediol found in the serum of alcoholics (Koop, D.R., Casazza, J.P.: J Biol Chem 260: 13607-13612, 1985). Specific polyclonal antibody against ethanol-inducible cytochrome P450 (P450j, P450 IIE) was prepared in rabbit and utilized to isolate cDNA for P450j. The cDNAs encoding P450j of both rat and human were isolated and characterized. The primary amino acid sequences of rat and human P450j were determined by nucleotide sequencing of the longest cDNAs for P450j; The rat P450j sequence was compared to those of other cytochrome P450s to determine the structural similarity. Cloned P450j cDNA and antibodies were used to study the expression of P450j gene during development and by various inducers as well as pathophysiological conditions. By combination of cDNA hybridization and immunoblot analyses, three types of P450j gene expression were observed: transcriptional activation during development; post-transcriptional activation (probably via protein stabilization) by various inducers such as ethanol, acetone, and pyrazole derivatives; and mRNA stabilization in diabetes and starved animals. Distribution and regulation of P450j in different tissues were also studied by using cloned P450j cDNA.