Low Molecular Weight Phospholipases A2 in Mammalian Brain and Neural Cells: Roles in Functions and Dysfunctions

Abstract

Several "low molecular weight" or "secretory" phospholipases A(2) isoforms may be expressed in mammalian neural cells. Indeed, mRNAs for GIB, GIIA, GIIE, GIII, GV, GX, and GXII were detected in brain tissues despite different levels. However, only the presence of GIB, GIIA, and GV proteins has been clearly demonstrated in neural cells or in the nervous tissue. Although the roles of GIB and GV in the nervous tissue are still elusive, there is evidence to support the involvement of GIIA in physiological and pathological events, including neurotransmission, long-term potentiation, and neuritogenesis. The neurotoxic effects of an increase in GIIA may be envisaged under pathological conditions associated with the activation of astrocytes during inflammation or through activation of neurons and enzymes due to the stimulation of the NMDA glutamate receptor. In the past, elevation of GIIA expression in many acute and chronic neurological diseases is well known. Although each neurodegenerative disease has a separate etiology, many share similar neurochemical common processes, such as excitotoxicity, oxidative stress, and mitochondrial dysfunction, phenomena where GIIA play an important role.

Effect of NGF on the Subcellular Localization of Group IIA Secretory Phospholipase A2 (GIIA) in PC12 Cells: Role in Neuritogenesis

“…GIB, GIIA, GIIC, GIID, GIIE, GIIF, GIII, GV, GX and GXII) and their structural and functional properties have been recently reviewed [13]. The present study demonstrates that treatment of PC12 cells with NGF causes a time-dependent change in the subcellular localization of endogenous GIIA, one of the sPLA 2 isoforms expressed by this cell type and present in most mammalian brain areas.…”

“…Several reports have suggested that Ca 2? -dependent low molecular weight PLA 2 s, generally referred to as ''secretory'' (sPLA 2 ) may be involved in neuritogenesis [9][10][11][12][13]. The assumption that sPLA 2 isoforms are involved in neurite outgrowth derives both from studies in which cultured cells were exposed to exogenous enzymes from fungi [14], insect [12], snake venoms [15] and from studies in which the specific isoform group X sPLA 2 (GX), was overexpressed in PC12 cells [9].…”

“…In PC12 cells and in other neural cell lines GIIA has a cytosolic and mitochondrial localization [18]. Several lines of evidence indicate the involvement of this isoform in the onset and/or aggravation of various neurological diseases (for review see [13]). …”

Lack of group X secreted phospholipase A2 increases survival following pandemic H1N1 influenza infection

“…sPLA 2 enzymes are implicated in lipid mediator release(52), degranulation (52), cellular proliferation (52), destruction of invading bacteria (52), viruses (41,49) and activation of intracellular signaling cascades (42). GX-sPLA 2 is expressed in alveolar macrophages and epithelial cells in the lungs of patients with pneumonia (46), neuronal cells (29), male reproductive organs (22) and atherosclerotic plaques (39), and is cleaved to its active form in inflamed tissues (45). …”

The Binding Mode of Cladocoran A to the Human Group IIA Phospholipase A2

“…Moreover, the latest findings on the oncogenic action of PLA 2 in prostate cancer and its association with neurological disease offers further motivation for finding new modulators of its function. [9,10] The marine environment is a rich source of molecules endowed with anti-PLA 2 properties, a number of which have shown potent and selective in vitro and in vivo anti-sPLA 2 activity. [11][12][13] One of the most widespread groups of constituents found in sessile organisms with a typical selective profile against secretory PLA 2 are the sesquiterpenes bearing a g-hydroxybutenolide ring, whose reference compound is manoalide.…”