Disease relevance of CYP4F2

• Here, we report that CYP4F2 is constitutively expressed in a human hepatoma cell line, HepG2, and is not induced by clofibrate [1].

High impact information on CYP4F2

• FLJ39501 encodes a protein which was found to be a cytochrome P450, family 4, subfamily F, polypeptide 2 homolog of the leukotriene B4-omega-hydroxylase (CYP4F2) and could catalyze the 20-hydroxylation of trioxilin A3 from the 12(R)-lipoxygenase pathway [2].
• Studies with individually expressed human recombinant P450 enzymes revealed that two P450 enzymes, i.e. CYP4F2 and CYP4F3B, participate in the omega-hydroxylation of VLCFAs [3].
• Sesamin potently inhibited tocopherol-omega-hydroxylase activity exhibited by CYP4F2 and rat or human liver microsomes [4].
• Immunocytochemistry showed CYP4F2 and CYP4A11 expression in only the S2 and S3 segments of proximal tubules in cortex and outer medulla [5].
• Moreover, vicinal diol from both C18-epoxides and EETs were omega-hydroxylated by liver microsomes and by CYP4F2 and CYP4F3 [6].

Biological context of CYP4F2

• Despite the monophasic nature of renal AA omega-hydroxylation kinetics, immunochemical studies revealed participation of two P450s, CYP4F2 and CYP4A11, since antibodies to these enzymes inhibited 20-HETE formation by 65 [5].
• However, the human CYP4F2 gene was mapped to chromosome 19 [7].
• The CYP4F2 gene contains at least 13 exons with its open reading frame being encoded from exon II to exon XIII [1].
• The 5' flanking sequence downstream from -165 of the CYP4F2 gene has 75% similarity to the corresponding region of the CYP4F3 gene [1].
• We sequenced a 6.7-kb genomic fragment of the human CYP4F2 gene that has the first five exons and 500 bp of the 5'-flanking region [8].

Anatomical context of CYP4F2

• Among recombinant P450 enzymes, CYP4F2 and CYP4F3B catalyzed mainly the omega-hydroxylation of C18-epoxides with an apparent Vmax of between 0.84 and 15.0 min(-1), whereas the apparent Vmax displayed by CYP4F3A, the isoform found in leukocytes, ranged from 3.0 to 21.2 min(-1) [6].
• Antibodies to CYP4F2 markedly inhibited (93.4 +/- 6%; n = 5) formation of 20-HETE by hepatic microsomes, whereas antibodies to CYP4A11 were much less inhibitory (13.0 +/- 9%; n = 5) [9].
• CYP4F3 and CYP4F2 catalyse the inactivation of leukotriene B4 (LTB4), a potent mediator of inflammation responsible for recruitment and activation of neutrophils [10].
• Peroxisome proliferators inhibit CYP4F2 gene promoter activity and cotransfection with PPARalpha or PPARalpha/RXRalpha can slightly attenuate this inhibition [8].
• The expression of cytochrome P450 4F2 mRNAs was detected in HepG2 and A549 cells, and thus the arachidonic acid and leukotriene B(4) omega-hydroxylation activities in the nuclear envelope fractions of HepG2 and A549 cells are likely due to cytochrome P450 4F2 [11].

Associations of CYP4F2 with chemical compounds

• Additionally, ketoconazole preferentially inhibited CYP4F2, but not CYP4F3B, and partially inhibited M1 formation by HLMs [12].
• Metabolism of arachidonic acid to 20-hydroxy-5,8,11, 14-eicosatetraenoic acid by P450 enzymes in human liver: involvement of CYP4F2 and CYP4A11 [9].
• Expression and molecular cloning of human liver leukotriene B4 omega-hydroxylase (CYP4F2) gene [1].
• Human liver leukotriene B4 (LTB4) omega-hydroxylase (CYP4F2) plays an important role in the metabolic inactivation and degradation of LTB4, a potent mediator of inflammation [1].
• Promoter activity and regulation of the CYP4F2 leukotriene B(4) omega-hydroxylase gene by peroxisomal proliferators and retinoic acid in HepG2 cells [8].

Other interactions of CYP4F2

• Our results demonstrate that CYP4F2 and CYP4A11 underlie conversion of AA to 20-HETE, a natriuretic and vasoactive eicosanoid, in human kidney [5].
• The deduced protein showed 81.2 and 76.7% amino acid identity with the human enzymes CYP4F2 and CYP4F3 [13].
• Further screening showed that recombinant CYP2J2, CYP4F2, and CYP4F3B could also catalyze M1 formation [12].
• The CYP4F11 gene is located 16 kb upstream of the CYP4F2 gene on chromosome 19 [14].
• CYP3A4 and CYP4F2 were suggested to be involved in tocopherol degradation [15].
• Chromatin immunoprecipitation experiments indicate that more SREBP-1 is associated with the CYP4F2 promoter after overexpression of nSREBP-1a [16].

Analytical, diagnostic and therapeutic context of CYP4F2

• The present study examined accumulation of the metal toxins cadmium (Cd) and lead (Pb) in relation to the abundance of cytochrome P450 4F2 (CYP4F2), CYP2E1 and concentrations of zinc and copper in liver and kidney samples using immunoblotting coupled with metal analysis [17].

References