Biochemistry and Physiology of Mammalian Secreted Phospholipases A₂

Abstract

Phospholipases A(2) (PLA2s) are esterases that hydrolyze the sn-2 ester of glycerophospholipids and constitute one of the largest families of lipid hydrolyzing enzymes. The mammalian genome contains 10 enzymatically active secreted PLA2s (sPLA2s) and two sPLA2-related proteins devoid of lipolytic enzymatic activity. In addition to the well-established functions of one of these enzymes in digestion of dietary phospholipids and another in host defense against bacterial infections, accumulating evidence shows that some of these sPLA2s are involved in arachidonic acid release from cellular phospholipids for the biosynthesis of eicosanoids, especially during inflammation. More speculative results suggest the involvement of one or more sPLA2s in promoting atherosclerosis and cancer. In addition, the mammalian genome encodes several types of sPLA2-binding proteins, and mounting evidence shows that sPLA2s may have functions related to binding to cellular target proteins in a manner independent of their lipolytic enzymatic activity.

Lp-PLA2 et sPLA2

“…L'athérosclérose est une pathologie complexe où sont intriqués des facteurs métaboliques et inflammatoires, à la fois dans le développement de la maladie et dans ses complications. Les phospholipases A2 (PLA2) forment une famille d'enzymes qui hydrolysent les acides gras estérifiés des glycérophospholipides en position sn-2, produisant ainsi des acides gras (comme l'acide arachidonique) et des lysophospholipides (comme la lysophosphatidylcholine) [5]. Les maladies cardiovasculaires représentent la première cause de mortalité dans le monde.…”

“…C'est la raison pour laquelle l'identification de nouveaux biomarqueurs est importante pour mieux stratifier les patients et développer des stratégies thérapeutiques ciblées. Dans cette revue, nous nous sommes intéres-sés essentiellement à la valeur pronostique de deux SYNTHÈSE REVUES athérogène des particules de LDL, favorisent la formation des cellules spumeuses et activent la réponse inflammatoire, indépendamment de leurs propriétés catalytiques [5]. Plus récemment, il a été montré a contrario que la phospholipase A2 du groupe X inhibe le développement de l'athérosclérose expérimentale (Figure 1) en bloquant la réponse lymphocytaire T CD4 + de type Th1 [14].…”

Genes encoding multiple forms of phospholipase A2 are expressed in immature forms of human leukemic blasts

“…The sPLA 2 family is implicated in several biological processes such as inflammation and host defense. 1,2 Nine isoenzymes have been identified. Among them sPLA 2 -IB is the pancreatic one.…”

“…The cPLA 2 family consisted of four members, cPLA 2 -IVA, cPLA 2 -IVB, cPLA 2 -IVC and cPLA 2 -IVD; cPLA 2 -IVA being the central regulator of stimulus-coupled cellular AA release. 1,2 The iPLA 2 (PLA 2 -VI) plays a major role in phospholipids remodeling.…”

“…3 Deregulated PLA 2 activity contributes to the pathogenesis of several malignancies including prostate cancer, ovarian carcinoma and colorectal adenocarcinoma. 1,2 The COX and lipoxygenase pathways of AA have been recently documented on immature leukemic blasts of patients with acute myeloid (AML) and acute lymphoid (ALL) leukemia. 4,5 Thus, freshly isolated AML and ALL blasts express COX-1, produce the AA metabolite prostaglandin E 2 , express functional EP 2 receptors and increase their growth in response to exogenously added prostaglandin E 2 .…”