5-Lipoxygenase: mechanisms of regulation

Olof Rådmark,Bengt Samuelsson

doi:10.1194/jlr.r800062-jlr200

Abstract

5-lipoxygenase (5-LO) catalyzes two steps in biosynthesis of leukotrienes (LTs), a group of lipid mediators of inflammation derived from arachidonic acid (AA). LT antagonists are used in treatment of asthma; more recently a potential role also in atherosclerosis has raised considerable interest. Furthermore, possible effects of 5-LO metabolites in relation to tumorigenesis have emerged. Thus, an understanding of the biochemistry of this lipoxygenase has potential implications for treatment of various diseases.

Highlights

5-Lipoxygenase (5-LO) catalyzes two steps in biosynthesis of leukotrienes (LTs), a group of lipid mediators of inflammation derived from arachidonic acid (AA)
LTA4 is further converted by LTA4 hydrolase to the dihydroxyacid LTB4, and by LTC4 synthases to the glutathione conjugate LTC4
Methylation-specific DNA sequencing showed that the 5-LO core promoter is completely methylated in the cell lines U-937 and HL-60TB, while it is unmethylated in HL-60 cells [8]

Summary

Introduction

5-Lipoxygenase (5-LO) catalyzes two steps in biosynthesis of leukotrienes (LTs), a group of lipid mediators of inflammation derived from arachidonic acid (AA). In vitro methylation of the promoter strongly inhibited activity in reporter genes assays, while treatment of U-937 and HL-60TB cells with the demethylating agent 5-aza-2ʼdeoxycytidine restored 5-LO expression. Regulate the access of transcription factors; ChIP analysis showed that the histone deacetylase inhibitor trichostatin A increased binding of Sp1/Sp3, as well as of RNA polymerase II to the core part of the 5-LO gene promoter, in Mono Mac 6 cells [11].

Results

Conclusion