Induction of cytochrome CYP4F3A in all-trans-retinoic acid-treated HL60 cells

Yoichi Mizukami, Hideki Sumimoto, Koichiro Takeshige

研究成果: ジャーナルへの寄稿学術誌査読

9 被引用数 (Scopus)


Cytochrome P-450 CYP4F3A catalyzes the inactivation of leukotriene B 4 by ω-hydroxylation, an activity of which is specifically expressed in human neutrophils. Here, we examined expression of the LTB 4 ω-hydroxylating activity during the differentiation of HL60 cells, an acute promyelocytic leukemia cell line, in the presence of various inducers. Among the inducers used, all-trans-retinoic acid (ATRA) most strongly induces the LTB4 ω-hydroxylating activity in a dose-dependent manner. The time course of the induction of the ω-hydroxylating activity correlates well with that of the superoxide-generating activity, indicative of cell differentiation. ATRA-treated cell microsomes convert LTB4 to its 20-hydroxyl derivative under aerobic conditions in the present of NADPH. The reaction is inhibited by carbon monoxide, an inhibitor of cytochrome P-450, and by antibodies raised against NADPH-P-450 reductase. CYP4F3A appears to be responsible for the LTB4 ω-hydroxylase activity, based on the following observations: expression of the mRNA for CYP4F3A is observed together with the induction of LTB4 ω-hydroxylating activity in ATRA-treated HL60 cells; and the apparent Km values for the ω-hydroxylation of LTB4 and lipoxin B4 by ATRA-treated cell microsomes are essentially the same as those of CYP4F3A in human neutrophil microsomes.

ジャーナルBiochemical and Biophysical Research Communications
出版ステータス出版済み - 1月 30 2004

!!!All Science Journal Classification (ASJC) codes

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学


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