Disease relevance of CYP4F8

• There was a prominent induction of CYP4F8 immunoreactivity and mRNA in psoriasis in comparison with unaffected epidermis of the same patients [1].

High impact information on CYP4F8

• Identification of CYP4F8 in human seminal vesicles as a prominent 19-hydroxylase of prostaglandin endoperoxides [2].
• Recombinant CYP4F8 oxygenated arachidonic acid to (18R)-hydroxyarachidonate, whereas prostaglandin (PG) D(2), PGE(1), PGE(2), PGF(2alpha), and leukotriene B(4) appeared to be poor substrates [2].
• Microsomes of human seminal vesicles oxygenated arachidonate, U-44069, U-46619, U-51605, and PGH(2), similar to CYP4F8 [2].
• We conclude that omega-side chain hydroxylation of PGH(2) analogues may be catalyzed by many different cytochromes P450, but only CYP4F8 oxidizes the omega-side chain of PGH(2) efficiently [3].
• Oxygenation of polyunsaturated long chain fatty acids by recombinant CYP4F8 and CYP4F12 and catalytic importance of Tyr-125 and Gly-328 of CYP4F8 [4].

Biological context of CYP4F8

• The missense mutation 374A>T of CYP4F8 (Tyr125Phe in substrate recognition site-1 (SRS-1)) occurs in low frequency [4].
• Single amino acid substitutions in SRS-1 and SRS-4 of CYP4F8 may thus influence oxygenation of certain substrates [4].
• Our aim was to determine the tissue distribution of CYP4F8, which occurs in human seminal vesicles and catalyzes 19-hydroxylation of prostaglandin H(1) and H(2) in vitro (J. Bylund, M. Hidestrard, M. Ingelman-Sundberg, E.H. Oliw, J. Biol. Chem. 275 (2000) 21844-21849) [1].
• The CYP4F8 transcripts were detected by reverse transcription polymerase chain reaction and by Northern blot analysis [1].

Anatomical context of CYP4F8

• CYP4F8 was found to metabolize U51605 to 90% of the (19R)-hydroxy metabolite, providing further evidence in favor of a role of CYP4F8 in biosynthesis of (19R)-hydroxy PGE in human seminal vesicles [3].
• We conclude that PGH synthase-2, CYP4F8, and PGE synthase-1 likely forms 19-hydroxy-PGE compounds in seminal vesicles and vas deferens, but the catalytic properties of CYP4F8 suggest additional biological functions [5].
• Screening of 50 human tissues for CYP4F8 immunoreactivity revealed protein expression, inter alia, in seminal vesicles, epidermis, hair follicles, sweat glands, corneal epithelium, proximal renal tubules, and epithelial linings of the gut and urinary tract [1].
• The function of CYP4F8 in epidermis might be related to lipid oxidation and keratinocyte proliferation [6].

Associations of CYP4F8 with chemical compounds

• Recombinant CYP4F8 catalyzes n-2 hydroxylation of PGH1 and PGH2 and n-3 hydroxylation of arachidonic acid [5].
• Recombinant CYP4F8 was also found to catalyze n-2 hydroxylation of PGI2 and carbaprostacyclin (Km to approximately 40 microM), and n-2 and n-3 hydroxylation of carbocyclic TXA2 [5].
• CYP4F8 is the first described hydroxylase with specificity and catalytic competence for prostaglandin endoperoxides [2].
• This variant oxidized two PGH2 analogs, U-51605 and U-44069, in analogy with CYP4F8, but 20:4n-6 and 22:5n-6 were not oxidized [4].
• CYP4F8 was found to catalyze epoxidation of docosahexaenoic acid (22:6n-3) and docosapentaenoic acid (22:5n-3) and omega3-hydroxylation of 22:5n-6 [4].

Other interactions of CYP4F8

• This cDNA contains an entire coding region of a 524-amino-acid protein that is 81.7, 78.3, and 78.2% identical to CYP4F2, CYP4F3, and CYP4F8, respectively [7].
• On the mechanism of biosynthesis of 19-hydroxyprostaglandins of human seminal fluid and expression of cyclooxygenase-2, PGH 19-hydroxylase (CYP4F8) and microsomal PGE synthase-1 in seminal vesicles and vas deferens [5].
• Recombinant CYP4F8 and CYP4F12 metabolize prostaglandin H2 (PGH2) analogs by omega2- and omega3-hydroxylation and arachidonic acid (20:4n-6) by omega3-hydroxylation [4].

Analytical, diagnostic and therapeutic context of CYP4F8

• Quantification by real-time PCR suggested that the transcripts of PGH synthase-2, CYP4F8, and microsomal PGE synthase-1 were abundant and correlated in seminal vesicles of seven patients (p < 0.05) [5].
• Polyclonal antibodies were raised in rabbits against RVEPLG, the C-terminal end of CYP4F8, and purified by affinity chromatography [1].

References