2015年2月
Functional characterization of 10 CYP4A11 allelic variants to evaluate the effect of genotype on arachidonic acid omega-hydroxylation
DRUG METABOLISM AND PHARMACOKINETICS
- 巻
- 30
- 号
- 1
- 開始ページ
- 119
- 終了ページ
- 122
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.dmpk.2014.09.001
- 出版者・発行元
- JAPANESE SOC STUDY XENOBIOTICS
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 CYP4A11 are associated with susceptibility to hypertension. In this study, we evaluated the in vitro omega-hydroxylation of arachidonic acid by 10 CYP4A11 allelic 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 omega-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. Copyright (C) 2014, The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.dmpk.2014.09.001
- ISSN : 1347-4367
- eISSN : 1880-0920
- Web of Science ID : WOS:000353285500014