Phosphorylation of 5-LOX: The Potential Set-point of Inflammation

Neurochem Res. 2020 Oct;45(10):2245-2257. doi: 10.1007/s11064-020-03090-3. Epub 2020 Jul 15.

Abstract

Inflammation secondary to tissue injuries serves as a double-edged sword that determines the prognosis of tissue repair. As one of the most important enzymes controlling the inflammation process by producing leukotrienes, 5-lipoxygenase (5-LOX, also called 5-LO) has been one of the therapeutic targets in regulating inflammation for a long time. Although a large number of 5-LOX inhibitors have been explored, only a few of them can be applied clinically. Surprisingly, phosphorylation of 5-LOX reveals great significance in regulating the subcellular localization of 5-LOX, which has proven to be an important mechanism underlying the enzymatic activities of 5-LOX. There are at least three phosphorylation sites in 5-LOX jointly to determine the final inflammatory outcomes, and adjustment of phosphorylation of 5-LOX at different phosphorylation sites brings hope to provide an unrecognized means to regulate inflammation. The present review intends to shed more lights into the set-point-like mechanisms of phosphorylation of 5-LOX and its possible clinical application by summarizing the biological properties of 5-LOX, the relationship of 5-LOX with neurodegenerative diseases and brain injuries, the phosphorylation of 5-LOX at different sites, the regulatory effects and mechanisms of phosphorylated 5-LOX upon inflammation, as well as the potential anti-inflammatory application through balancing the phosphorylation-depended set-point.

Keywords: 5-Lipoxygenase; Arachidonate; Inflammation; Leukotrienes; Phosphorylation.

Publication types

  • Review

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / chemistry
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Brain / enzymology
  • Brain / metabolism
  • Brain Injuries / enzymology
  • Brain Injuries / metabolism*
  • Humans
  • Inflammation / enzymology
  • Inflammation / metabolism*
  • Lipoxygenase Inhibitors / pharmacology
  • Neurodegenerative Diseases / enzymology
  • Neurodegenerative Diseases / metabolism*
  • Phosphorylation / drug effects
  • Phosphorylation / physiology
  • Serine / chemistry

Substances

  • Lipoxygenase Inhibitors
  • Serine
  • Arachidonate 5-Lipoxygenase