Abstract
Cytochrome P450 2J2 (CYP2J2) is a known arachidonic acid (AA) epoxygenase that mediates the formation of four bioactive regioisomers of cis-epoxyeicosatrienoic acids (EETs). Although its expression in the liver is low, CYP2J2 is mainly observed in extrahepatic tissues, including the small intestine, pancreas, lung, and heart. Changes in CYP2J2 levels or activity by xenobiotics, disease states, or polymorphisms are proposed to lead to various organ dysfunctions. Several studies have investigated the regulation of CYP2J2 and EET formation in various cell lines and have demonstrated that such regulation is tissue-dependent. In addition, studies linking CYP2J2 polymorphisms to the risk of developing cardiovascular disease (CVD) yielded contradictory results. This review will focus on the mechanisms of regulation of CYP2J2 by inducers, inhibitors, and oxidative stress modeling certain disease states in various cell lines and tissues. The implication of CYP2J2 expression, polymorphisms, activity and, as a result, EET levels in the pathophysiology of diabetes and CVD will also be discussed.
Highlights
Cytochrome P450 (CYP) is a superfamily of membrane-bound, NADPH-dependent hemecontaining monooxygenases involved in the oxidation of both xenobiotics and endogenous compounds
There is mounting data supporting the protective role Cytochrome P450 2J2 (CYP2J2) plays in cardiovascular disease (CVD) and diabetes
Most of the evidence for protection stems from the transgenic mouse model with human CYP2J2 overexpression in the cardiomyocytes but not the endothelial cells
Summary
Cytochrome P450 (CYP) is a superfamily of membrane-bound, NADPH-dependent hemecontaining monooxygenases involved in the oxidation of both xenobiotics and endogenous compounds. CYP epoxygenases, mainly the CYP2C sub-family and CYP2J2, are reported to form exclusively one or more of the four possible cis-EETs. Several other isozymes including CYP3A4, CYP1A1, Int. J. GPR40 is expressed primarily in the pancreas and the brain, at both the mRNA and protein levels [56,57], as well as in the liver, heart, and skeletal muscle at an mRNA level [56,58] While this finding is exciting and the first report identifying an “EET receptor” more work is needed to determine if the GPR40 is the receptor for EETs in cardiomyocytes. We will present genetic associations of CYP2J2 polymorphisms with related outcomes in humans
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