The Functions of Five Distinct Mammalian Phospholipase A2s in Regulating Arachidonic Acid Release

Role of sphingomyelin and ceramide in the regulation of the activity and fatty acid specificity of group V secretory phospholipase A2

“…Unlike sPLA 2 IIa, however, sPLA 2 V binds efficiently to the major phospholipid (PC) in membranes and lipoproteins [10], and therefore may be physiologically more relevant in phospholipid turnover and eicosanoid synthesis. Balboa et al [8] showed that the arachidonate release and prostaglandin production in mouse macrophage cell line P388D was dependent upon the presence of sPLA 2 V. Similarly, Murakami et al [11] reported that in fibroblasts and CHO cells, sPLA 2 V acts in concert with the cytosolic PLA 2 in the release of arachidonate. sPLA 2 V also has strong affinity to proteoglycans on the cell surface, and this property appears to be critical for its function [11].…”

“…Balboa et al [8] showed that the arachidonate release and prostaglandin production in mouse macrophage cell line P388D was dependent upon the presence of sPLA 2 V. Similarly, Murakami et al [11] reported that in fibroblasts and CHO cells, sPLA 2 V acts in concert with the cytosolic PLA 2 in the release of arachidonate. sPLA 2 V also has strong affinity to proteoglycans on the cell surface, and this property appears to be critical for its function [11]. The enzyme has been reported to be present in atherosclerotic lesions [28], and may be involved in the conversion of LDL to a more atherogenic particle [29].…”

“…The group V enzyme (sPLA 2 V) is expressed in heart, lung, placenta, spleen and macrophages [8;10]. This enzyme can also induce eicosanoid synthesis in various inflammatory cells including neutrophils and eosinophils [10], and acts in concert with the cytosolic PLA 2 in releasing the arachidonate [11]. The physiological factors involved in the regulation of this enzyme activity are not known.…”

N‐terminal and C‐terminal plasma membrane anchoring modulate differently agonist‐induced activation of cytosolic phospholipase A2

“…These chimeras were expressed in Chinese hamster ovary (CHO) cells overproducing the G-protein-coupled a 2B adrenergic receptor (CHO-2B cells). CHO cells contain three forms of PLA 2 s, like many other cell types, and they seem to play different roles in D 4 Ach release: an sPLA 2 , which is not involved in rapid receptor-mediated D 4 Ach release [4,21], an iPLA 2 [22], which q FEBS 1999 is mainly involved in the remodeling of membrane phospholipids [23], and cPLA 2 , which is responsible for D 4 Ach release after stimulation by extracellular agonists or an increase in intracellular Ca 2+ [4,5]. In CHO-2B cells it was possible to separately induce receptor-mediated phosphorylation and activation of cPLA 2 by Ca 2 [24].…”

“…Recent evidence indicates that cPLA 2 plays a major role in the overproduction of lipid mediators during inflammation [2,3]. cPLA 2 activated by extracellular stimuli triggers the rapid hydrolysis of membrane phospholipids to give free arachidonic acid (D 4 Ach), which is the rate-limiting step of eicosanoid production [4,5]. This activation is dependent on at least two mechanisms: the phosphorylation of cPLA 2 by various kinases and its translocation to membrane phospholipids by a Ca 2+ -dependent lipid-binding domain (CaLB domain) [6], following an increase in intracellular Ca 2+.…”