Group X secreted phospholipase A2 (sPLA2-X)

Group X secreted phospholipase A2 (sPLA2-X), encoded by the PLA2G10 gene, is a highly active member of the secreted phospholipase A2 family known for its potent ability to hydrolyze phosphatidylcholine-rich mammalian cell membranes (UniProt, https://www.uniprot.org/uniprotkb/P54070/entry). It functions by cleaving the sn-2 ester bond of phospholipids, releasing free fatty acids like arachidonic acid and lysophospholipids, which are essential precursors for pro-inflammatory eicosanoids such as prostaglandins and leukotrienes (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414650/). Beyond its role in lipid mediator production, sPLA2-X is involved in diverse biological processes including sperm capacitation, lipid droplet formation, and the regulation of cell survival pathways (Wikipedia, https://en.wikipedia.org/wiki/Phospholipase_A2; NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156874/). Pathologically, it is strongly associated with inflammatory conditions like asthma and atherosclerosis, as well as various cancers where it promotes tumor cell proliferation and resistance to apoptosis (MDPI, https://www.mdpi.com/1422-0067/21/19/4459; NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414650/). In cardiovascular disease, sPLA2-X contributes to the modification of low-density lipoproteins (LDL), facilitating their uptake by macrophages and the formation of foam cells (NIH, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414650/). Therapeutic targeting of sPLA2-X has been explored using small-molecule inhibitors such as varespladib, which aim to reduce systemic inflammation and lipid-driven damage (OAText, https://www.oatext.com/Phospholipase-A2-enzymes-and-the-risk-of-atherosclerosis.php). However, clinical development has faced significant hurdles, including a lack of efficacy in major cardiovascular trials and concerns regarding the broad inhibition of multiple sPLA2 isoforms (Journal of the American College of Cardiology, https://www.jacc.org/doi/10.1016/j.jacc.2010.06.029).

Other names

PLA2G10Phosphatidylcholine 2-acylhydrolase 10Secretory phospholipase A2 group XhGX sPLA2

Inhibition of the enzymatic hydrolysis of the sn-2 ester bond in phospholipids, thereby preventing the release of arachidonic acid and the subsequent production of pro-inflammatory eicosanoids.