Rapid regulation of neurite outgrowth and retraction by phospholipase A2-derived arachidonic acid and its metabolites

Smalheiser, Neil R.; Dissanayake, Shehan; Kapil, Aditya

doi:10.1016/0006-8993(96)00134-5

Cited by 65 publications

(26 citation statements)

References 51 publications

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“…observation is supported by studies on the effect of PLA 2 inhibitors that are known to exert a biphasic effect over several days on elongation in dorsal root ganglion axon, enhancing outgrowth at low concentrations and inhibiting outgrowth at higher concentration [38]. It is interesting to note here that cPLA 2 inhibitors delay the initial outgrowth of neurites on laminin and exogenous arachidonic acid enhances neurite outgrowth [39]. Also, interphase cells release arachidonic acid in response to agonists, and this release is strongly inhibited in mitotic cells [40].…”

Section: Nuclear Pla 2 Activitiessupporting

confidence: 63%

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

Farooqui

Horrocks

2005

Reprod. Nutr. Dev.

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-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

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Section: Nuclear Pla 2 Activitiessupporting

confidence: 63%

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

Farooqui

Horrocks

2005

Reprod. Nutr. Dev.

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“…The treatment of NG 108-15 cells with AACOCF 3 decreases initial neurite formation in a concentrationdependent manner (Smalheiser et al, 1996). The pharmacological blockade of cPLA 2 by a low concentration, 10 M, of AACOCF 3 significantly inhibits neuronal death in the CA1 region of rat hippocampus.…”

Section: A Arachidonyl Trifluoromethyl Ketonementioning

confidence: 89%

Inhibitors of Brain Phospholipase A₂Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders

Farooqui

Ong²,

Horrocks³

2006

Pharmacol Rev

341

246

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“…Thus, arachidonate is involved in long-term potentiation (LTP) and neuritogenesis (Smalheiser et al, 1996), lysophospholipids and prostaglandins are involved in neurotransmitter release, and high levels of arachidonic acid and lysophospholipids are associated with neurodegeneration (see below). Normally, arachidonate and lysophospholipids are recycled through a series of energy-dependent reactions (Fig.…”

Section: Biological Effects Of Pla2-catalyzed Reaction Productsmentioning

confidence: 99%

Phospholipase A₂ and Its Role in Brain Tissue

Farooqui

Yang

Rosenberger

et al. 1997

Journal of Neurochemistry

325

202

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Phospholipase A2 (PLA2) is the name for the class of lipolytic enzymes that hydrolyze the acyl group from the sn-2 position of glycerophospholipids, generating free fatty acids and lysophospholipids. The products of the PLA2-catalyzed reaction can potentially act as second messengers themselves, or be further metabolized to eicosanoids, platelet-activating factor, and lysophosphatidic acid. All of these are recognized as bioactive lipids that can potentially alter many ongoing cellular processes. The presence of PLA2 in the central nervous system, accompanied by the relatively large quantity of potential substrate, poses an interesting dilemma as to the role PLAS has during both physiologic and pathologic states. Several different PLA2 enzymes exist in brain, some of which have been partially characterized. They are classified into two subtypes, Ca 2~-dependentand Ca2-independent, based on their catalytic dependence on Ca~.Under physiologic conditions, PLA 2 may be involved in phospholipid turnover, membrane remodeling, exocytosis, detoxification of phospholipid peroxides, and rieurotransmitter release. However, under pathological situations, increased PLA2 activity may result in the loss of essential membrane glycerophospholipids, resulting in altered membrane permeability, ion homeostasis, increased free fatty acid release, and the accumulation of lipid peroxides. These processes, along with loss of ATP, may be responsible for the loss of membrane phospholipid and subsequent neuronal injury found in ischemia, spinal cord injury, and other neurodegenerative diseases. This review outlines the current knowledge of the PLA2 found in the central nervous system and attempts to define the role of PLA2 during both physiologic and pathologic conditions.

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Rapid regulation of neurite outgrowth and retraction by phospholipase A2-derived arachidonic acid and its metabolites

Cited by 65 publications

References 51 publications

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

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

Inhibitors of Brain Phospholipase A₂Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders

Phospholipase A₂ and Its Role in Brain Tissue

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Rapid regulation of neurite outgrowth and retraction by phospholipase A2-derived arachidonic acid and its metabolites

Cited by 65 publications

References 51 publications

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

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

Inhibitors of Brain Phospholipase A2Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders

Phospholipase A2 and Its Role in Brain Tissue

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Product

Resources

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Inhibitors of Brain Phospholipase A₂Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders

Phospholipase A₂ and Its Role in Brain Tissue