Deduced amino acid sequence of a murine cytochrome P-450 Cyp4a protein: developmental and hormonal regulation in liver and kidney.
Proteins from the cytochrome P-450 CYP4A gene family metabolise hormones such as prostaglandins and other fatty acids, and are induced by peroxisome proliferators such as the hypolipidaemic drugs clofibrate and ciprofibrate. In order to better understand the function and regulation of these enzymes we have cloned a murine cDNA, Cyp4a-10, whose deduced amino acid sequence shares 92% sequence identity with rat CYP4A1. The developmental and hormonal regulation of this protein and other members of the murine Cyp4a gene family were then studied using a polyclonal antibody to rat CYP4A1. The expression of Cyp4a proteins in liver and kidney develop gradually from birth and are sexually differentiated in mature animals; growth hormone appears to be involved in regulating expression of hepatic Cyp4a proteins. The administration of phenobarbital and dexamethasone affected the expression of Cyp4a proteins in the liver, but not in the kidney, where testosterone was the key regulatory factor, demonstrating interesting tissue-specific effects in the regulation of these enzymes.
Imperial Cancer Research Fund, Ninewells Hospital and Medical School, Dundee, UK.
C J
CJ
Henderson
T
T
Bammler
C R
CR
Wolf
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics*; D018076:DNA, Complementary / Q000302:isolation & purification; D005260:Female; D005786:Gene Expression Regulation; D007016:Hypophysectomy; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid; D012737:Sex Factors
D018076:DNA, Complementary; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A