Signaling and interplay mediated by phospholipases A2, C, and D in LA-N-1 cell nuclei

Abstract

-Phospholipids are integral components of the nuclear membranes and intranuclear domains. Alterations in phospholipid metabolism occur during cellular differentiation, proliferation, and apoptosis, but the molecular mechanism involved in the above processes remains unknown. We propose that the coordinated expression of different genes responsible for the expression of transcription factors, neurotrophins, and cytokines, along with lipid mediators generated by the action of phospholipases A 2 , C, and D (PLA 2 , PLC, and PLD), play a very important role in differentiation, proliferation, and apoptosis. The purpose of this minireview is to discuss recent developments in PLA 2 , PLC, and PLD-mediated signaling in the nucleus of LA-N-1 neuroblastoma cell cultures. In brain tissue, arachidonic acid is mainly released by the action of PLA 2 and phospholipase C/diacylglycerol lipase (PLC/DAG-lipase) pathways. We have used LA-N-1 cell cultures to study activities of PLA 2 , C, and D during retinoic acid (RA)-mediated differentiation. The treatment of LA-N-1 cells with RA produces an increase in PLA 2 activity in the nuclear fraction. This increase in PLA 2 activity can be prevented with BMS493, a pan retinoic acid receptor antagonist, suggesting that RA-induced stimulation of PLA 2 activity is a RA receptor-mediated process. The treatment of LA-N-1 cells with 12-O-tetradecanoyl-phorbol-13 acetate (TPA) and RA increases diacylglycerol (DAG) levels indicating the stimulation of PLC activity. This stimulation is blocked by D609, tricyclodecan-9-yl potassium xanthate, a competitive PtdCho-specific PLC inhibitor. LA-N-1 cells also contain DAG-and monoacylglycerol (MAG) lipase activities. Two isoforms of PLD, oleate-dependent and TPA-dependent, are also present in LA-N-1 cell homogenates. RA stimulates the oleate-dependent isoform of PLD, whereas RA does not stimulate the TPA-dependent isoform. Our studies have indicated that lipid mediators generated by the action of PLA 2 , PLC, and PLD on nuclear phospholipids markedly affect neuritic outgrowth and neurotransmitter release in cells of neuronal and glial origin. We propose that RA receptors coupled with PLA 2 , PLC, and PLD activities in the nucleus may play an important role in the redistribution of arachidonic acid and its metabolites and DAG in nuclear and nonnuclear neuronal membranes during differentiation and growth suppression. nucleus / phospholipase A 2 / phospholipase C / phospholipase D / arachidonic acid / eicosanoids / peroxisome proliferators activated receptor

Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis

“…It is suggested that this may be achieved with the assistance of at least one of three different enzymes, namely phospholipase A 2 (PLA 2 ), phospholipase C and phospholipase D [7]. PLA 2 , however, is the only phospholipase that seems to be able to release free AA directly in a single-step reaction, by hydrolysing an ester bond at the sn-2 position of phospholipids [8], which is why it features as the main phospholipase of interest in most literature in connection with AA metabolism.…”

Edema Induced by a Crotalus durissus terrificus Venom Serine Protease (Cdtsp 2) Involves the PAR Pathway and PKC and PLC Activation

“…The COX-2 enzyme catalyzes the conversion of AA into various prostaglandins, such as PGE2, which are associated with an increase in the synthesis of proinflammatory cytokines, tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β). Furthermore, these mediators are formed following the hydrolytic action of PLA2 on cell membrane phospholipids, resulting in the release of AA, as well as the production of other metabolites such as 8-isoprostanes, which can undergo nonenzymatic peroxidation via intermediate reactive oxygen species [14,18,29,30,31,32,33,34,35]. …”

“…Other cPLA2 enzymes include diacylglycerol (DAG), which is involved in protein kinase C (PKC) and phospholipase C (PLC) activation. This activation is responsible for the production of inositol triphosphate (IP 3 ) and DAG [18,19,20,21]. Notwithstanding, PKC and PLC are also key elements in pathway signaling mediated by protease-activated receptors (PARs).…”

The necessity of adequate nutrition with diets containing omega-3 and omega-6 fatty acids for proper brain development, function and delayed aging: Review

“…It has also been shown that phospholipases A2, C, and D are important participants in the signaling and interplay of different metabolic and signal pathways in LA-N-1 cell nuclei (Farooqui and Horrocks, 2005).…”