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Functional characterization of 10 CYP4A11 allelic variants to evaluate the effect of genotype on arachidonic acid ω-hydroxylation.
Saito, Takahiro; Honda, Masashi; Takahashi, Masamitsu; Tsukada, Chiharu; Ito, Miyabi; Katono, Yuki; Hosono, Hiroki; Saigusa, Daisuke; Suzuki, Naoto; Tomioka, Yoshihisa; Hirasawa, Noriyasu; Hiratsuka, Masahiro.
Afiliação
  • Saito T; Laboratory of Pharmacotherapy of Life-Style Related Disease, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Honda M; Laboratory of Pharmacotherapy of Life-Style Related Disease, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Takahashi M; Laboratory of Pharmacotherapy of Life-Style Related Disease, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Tsukada C; Laboratory of Pharmacotherapy of Life-Style Related Disease, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Ito M; Laboratory of Pharmacotherapy of Life-Style Related Disease, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Katono Y; Laboratory of Pharmacotherapy of Life-Style Related Disease, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Hosono H; Laboratory of Pharmacotherapy of Life-Style Related Disease, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Saigusa D; Department of Integrative Genomics, Tohoku Medical Megabank, Tohoku University, Sendai, Japan.
  • Suzuki N; Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Tomioka Y; Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Hirasawa N; Laboratory of Pharmacotherapy of Life-Style Related Disease, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
  • Hiratsuka M; Laboratory of Pharmacotherapy of Life-Style Related Disease, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. Electronic address: mhira@m.tohoku.ac.jp.
Drug Metab Pharmacokinet ; 30(1): 119-22, 2015 Feb.
Article em En | MEDLINE | ID: mdl-25760539
ABSTRACT
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 ω-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 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Araquidônico / Polimorfismo de Nucleotídeo Único / Sistema Enzimático do Citocromo P-450 / Alelos Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Araquidônico / Polimorfismo de Nucleotídeo Único / Sistema Enzimático do Citocromo P-450 / Alelos Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article