Prostaglandin and leukotriene metabolism in senescence (Homo sapiens)
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Description
LTD4 is of particular importance in cellular senescence due to its increased interaction with the cysteinyl leukotriene receptor 1 (CysLT1R) (Wei et al., 2018; Song et al., 2019). This interaction has various consequences, such as the release of intracellular Ca2+, an increase of p21 and it also inhibits sirtuin 1 (SIRT1). SIRT1 regulates the cell cycle by inhibiting the phosphorylation of p53 and the release of various cytokines (Wei et al., 2018). Therefore, it increases the release of pro-inflammatory cytokines and induce cellular senescence via the activation of p53 (Song et al., 2019).
ALOX5 contributes to an increase in reactive oxygen species (ROS) (Catalano et al., 2005; Menna et al., 2010). These ROS are thought to activate p53 which binds to ALOX5 and further increases its action (Häfner et al., 2019). Moreover, ALOX5 uses Ca2+ as a cofactor and its increased intracellular concentration further promotes ALOX5's action (Menna et al., 2010). LTB4 is also stimulates the production of ROS. ALOX5 then stimulates the phosphorylation of p53 and activates p21 (Menna et al., 2010; Catalano et al., 2005). This then causes the dephosphorylation of the retinoblastoma protein (RB1). As a consequence, senescence is induced (Catalano et al., 2005).
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- Lin Y, Xu Z; ''Fibroblast Senescence in Idiopathic Pulmonary Fibrosis.''; Front Cell Dev Biol, 2020 PubMed Europe PMC Scholia
- Wei J, Chen S, Guo W, Feng B, Yang S, Huang C, Chu J; ''Leukotriene D4 induces cellular senescence in osteoblasts.''; Int Immunopharmacol, 2018 PubMed Europe PMC Scholia
- Suryadevara V, Ramchandran R, Kamp DW, Natarajan V; ''Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways.''; Int J Mol Sci, 2020 PubMed Europe PMC Scholia
- Catalano A, Rodilossi S, Caprari P, Coppola V, Procopio A; ''5-Lipoxygenase regulates senescence-like growth arrest by promoting ROS-dependent p53 activation.''; EMBO J, 2005 PubMed Europe PMC Scholia
- Wiley CD, Sharma R, Davis SS, Lopez-Dominguez JA, Mitchell KP, Wiley S, Alimirah F, Kim DE, Payne T, Rosko A, Aimontche E, Deshpande SM, Neri F, Kuehnemann C, Demaria M, Ramanathan A, Campisi J; ''Oxylipin biosynthesis reinforces cellular senescence and allows detection of senolysis.''; Cell Metab, 2021 PubMed Europe PMC Scholia
- Cormenier J, Martin N, Deslé J, Salazar-Cardozo C, Pourtier A, Abbadie C, Pluquet O; ''The ATF6α arm of the Unfolded Protein Response mediates replicative senescence in human fibroblasts through a COX2/prostaglandin E2intracrine pathway.''; Mech Ageing Dev, 2018 PubMed Europe PMC Scholia
- Yang HH, Kim C, Jung B, Kim KS, Kim JR; ''Involvement of IGF binding protein 5 in prostaglandin E(2)-induced cellular senescence in human fibroblasts.''; Biogerontology, 2011 PubMed Europe PMC Scholia
- Häfner AK, Kahnt AS, Steinhilber D; ''Beyond leukotriene formation-The noncanonical functions of 5-lipoxygenase.''; Prostaglandins Other Lipid Mediat, 2019 PubMed Europe PMC Scholia
- Wiley CD, Brumwell AN, Davis SS, Jackson JR, Valdovinos A, Calhoun C, Alimirah F, Castellanos CA, Ruan R, Wei Y, Chapman HA, Ramanathan A, Campisi J, Jourdan Le Saux C; ''Secretion of leukotrienes by senescent lung fibroblasts promotes pulmonary fibrosis.''; JCI Insight, 2019 PubMed Europe PMC Scholia
- Menna C, Olivieri F, Catalano A, Procopio A; ''Lipoxygenase inhibitors for cancer prevention: promises and risks.''; Curr Pharm Des, 2010 PubMed Europe PMC Scholia
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