Phosphorylation of 5-LOX: The Potential Set-point of Inflammation
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REVIEW
Phosphorylation of 5‑LOX: The Potential Set‑point of Inflammation Zonglin He1,2 · Di Tao1,2 · Jiaming Xiong1 · Fangfang Lou1 · Jiayuan Zhang1 · Jinxia Chen1 · Weixi Dai1,2 · Jing Sun1 · Yuechun Wang1 Received: 13 February 2020 / Revised: 11 June 2020 / Accepted: 6 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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 · Phosphorylation · Arachidonate · Leukotrienes · Inflammation Abbreviations FDA Food and Drug Administration CNS Central nervous systems AA Arachidonic acid FLAP 5-Lipoxygenase-activating protein LOX Lipoxygenase LT Leukotriene cPLA2 Cytosolic phospholipase A2 LTA4 Leukotriene A4 LTB4 Leukotriene B4 LTC4 Leukotriene C4 LTD4 Leukotriene D4 iNOS Inducible nitric oxide synthase PTM Post-translational modification
* Yuechun Wang [email protected]; [email protected] 1
Department of Physiology, Basic Medical School, Jinan University, Huangpu Avenue 601, Tianhe District, Guangzhou, Guangdong Province, China
Faculty of Medicine, International school, Jinan University, Huangpu Avenue 601, Tianhe District, Guangzhou, Guangdong Province, China
2
TBI Traumatic brain injury AD Alzheimer’s disease Aβ Amyloid beta NFT Neurofibrillary tangles NSC Neural stem cell CLP Coactosin-like protein BMMC Mouse bone marrow-derived mast cells PKA Protein kinase A CaMKII Ca2 + /calmodulin-dependent kinase MAPKAPK Mitogen-activated protein kinase-activated protein kinase MAP Mitogen-activated protein MK Mitogen kinase (AP kinase) COX Cyclooxygenase cPLA2 Cytosolic phospholipase A2 PG Prostaglandin PMNL Pol
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