| Autor: |
Saito, Takahiro, Honda, Masashi, Takahashi, Masamitsu, Tsukada, Chiharu, Ito, Miyabi, Katono, Yuki, Hosono, Hiroki, Saigusa, Daisuke, Suzuki, Naoto, Tomioka, Yoshihisa, Hirasawa, Noriyasu, Hiratsuka, Masahiro |
| Zdroj: |
Drug Metabolism and Pharmacokinetics; February 2015, Vol. 30 Issue: 1 p119-122, 4p |
| Abstrakt: |
Genetic variations in cytochrome P450 4A11 (CYP4A11) contributes to inter-individual variability in the metabolism of fatty acids such as arachidonic acid. CYP4A11 metabolizes arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), which is important for the regulation of blood pressure. Polymorphisms in CYP4A11are associated with susceptibility to hypertension. In this study, we evaluated the in vitroω-hydroxylation of arachidonic acid by 10 CYP4A11allelic variants, which cause amino acid substitutions in the encoded proteins. CYP4A11 variants were heterologously expressed in COS-7 cells and the kinetic parameters of arachidonic acid ω-hydroxylation were estimated. Among 10 CYP4A11 variants, 5 (CYP4A11-v1, CYP4A11-v2, CYP4A11-v3, CYP4A11-v4, and CYP4A11-v7) showed no or markedly lower activity compared to wild-type CYP4A11. This functional analysis of CYP4A11 variants could provide useful information for the effective prevention and treatment of hypertension. |
| Databáze: |
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