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Regulation of cyp4a31 by AMP‐activated protein kinase and peroxisome proliferator activated receptor alpha
Author(s) -
Bumpus Namandje,
Savas Uzen,
Johnson Eric F
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.757.13
Subject(s) - medicine , endocrinology , ampk , fenofibrate , amp activated protein kinase , peroxisome proliferator activated receptor , messenger rna , protein kinase a , activator (genetics) , chemistry , gene expression , lipid metabolism , receptor , peroxisome , peroxisome proliferator activated receptor alpha , kinase , biology , nuclear receptor , gene , transcription factor , biochemistry
AMP‐activated protein kinase (AMPK) serves as asensor of cellular stress and is an important modulator of lipid and glucose metabolism. The present studies tested the ability of the AMPK activator aminoimidazole‐4‐carboxyamide‐ribonucleoside (AICAR) to regulate murine cyp4 gene expression. Hepatic cyp4 genes were screened for changes in mRNA levels following i.p. injection of eight‐week old C57BL/6 mice with AICAR relative to saline‐treated controls. The largest effect of AICAR 24 hours following injection was on cyp4a31 mRNA expression (3.5‐ and 5.5‐fold increase in males and females, respectively; p<0.01). Chronic injection of males with AICAR resulted in a 2.5‐fold increase of cyp4a31 mRNA (p<0.05) and a 3‐fold increase in lauric acid metabolism (p< 0.01) by liver microsomes prepared from the mice. Since information regarding the regulation of cyp4a31 has yet to be reported we investigated the effect of known regulators of the cyp4a family on the expression of cyp4a31. Cyp4a31 mRNA was markedly increased by treatment of mice with fenofibrate (50‐fold; p<0.01). However, fenofibrate treatment did not increase hepatic cyp4a31 mRNA in PPARα −/− mice. Similarly, preliminary studies demonstrate that cyp4a31 mRNA is not induced by AICAR in PPARα −/− suggesting a role for PPARα in the AICAR‐mediated induction of cyp4a31 . (Supported by HD004445 and fellowships from UNCF/Merck and the Fletcher Jones Foundation).