Ascorbic acid deficiency decreases the expression of CYP4A1 in liver microsomes of guinea pigs.
The cytochrome P-450 monooxygenase system plays a central role in the oxidation of a wide variety of structurally unrelated compounds. Its contribution is affected by nutritional and several other factors. Ascorbic acid (AA) deficiency decreases the content of cytochrome P-450 in liver microsomes of guinea pigs (GPs). Included in the group of cytochromes P-450 are the phenobarbital and 3-methylcholanthrene inducible moieties. In the present study the effect of AA status on another specific cytochrome P-450, CYP4A1, laurate omega-hydroxylase was investigated. Ascorbic acid may selectively increase or decrease certain forms of cytochromes. For four weeks adult male Hartley GPs were fed a diet containing 2.5 (Group I), 0.1 (Group II) and 0% (Group III) AA. The liver microsomes were isolated at this stage and cytochrome P-450 content was determined. Group III showed a significant decrease in cytochrome P-450 compared to groups I and II. They also showed a marked decrease in aminopyrine N-demethylase activity. The expression of CYP4A1 was evaluated using Western blot and anti-CYP4A1 antibody. Group III GPs showed a marked decrease in CYP4A1 expression. Groups I and II showed similar expression. This study demonstrates that CYP4A1, a specific cytochrome induced by hypolipidemic agents, is decreased by AA deficiency.
Roomi
M W
MW
Linus Pauling Institute of Science and Medicine, Palo Alto, CA, USA.
Ogg
M
M
Tsao
C S
CS
Gibson
G G
GG
D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000097:blood; D001206:Ascorbic Acid Deficiency / Q000097:blood / Q000201:enzymology*; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; D001205:Ascorbic Acid