Calcium-sensitive cytosolic phospholipase A2 (cPLA2) is expressed in human brain astrocytes

Stephenson, Diane; Manetta, Joseph; White, Donald L.; Chiou, X. Grace; Cox, Laura M.; Gitter, Bruce D.; May, Patrick C.; Sharp, John; Kramer, Ruth M.; Clemens, James A.

doi:10.1016/0006-8993(94)91221-1

Cited by 83 publications

(38 citation statements)

References 56 publications

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“…This availability depends on the activity of phospholipases, primarily PLA2. Both cPLA2 and secreted phospholipase can catalyze the release of AA (Dennis, 1994) and are detected in astrocytes (Oka and Arita, 1991;Stephenson et al, 1994).Our data show that both astrocytes and neurons express cPLA2 and that this expression is regulated by a factor(s) in the serum. It is interesting that neurons express lower amounts of cPLA2 and produce less POE2 than astrocytes even though both cell types express similar amounts of COX.…”

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confidence: 55%

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Transforming Growth Factor β1 Regulates the Expression of Cyclooxygenase in Cultured Cortical Astrocytes and Neurons

Luo¹,

Lang²,

Miller

1998

Journal of Neurochemistry

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Abstract:The hypothesis that transforming growth factor ßl (TGFß1) regulates the synthesis of prostaglandins by CNS tissue was tested by using purified cultures of cortical astrocytes or neurons that were obtained from rat pups on postnatal day 4 or 5 or fetuses on gestational day 16, respectively. The cells were exposed to TGFß1 for 2 days. The synthesis of prostaglandins depends upon the production and conversion of arachidonic acid, steps that are catalyzed by phospholipase A 2 (PLA2) and cyclooxygenase (COX), respectively. Prostaglandin E2 (PGE2) concentration was determined by radioimmunoassay. The expression of cytosolic PLA2 and COX (the constitutive COX1 and the inducible COX2) was assessed by using immunohistochemical and quantitative immunoblotting procedures. Astrocytes produced much more PGE2 than neurons, suggesting that glial cells are an important source of PGE2 in the CNS. TGF/31 increased the production of PGE2 by astrocytes and neurons in a concentration-dependent manner. Furthermore, TGFß1 enhanced COX activity; the inhibitor indomethacin completely blocked TGF/31-mediated PGE2 synthesis. Cultured astrocytes and neurons expressed the three enzymes: cytosolic PLA2, COX1, and COX2. Cytosolic PLA2 expression was unaffected by TGFf31 treatment. In contrast, COX expression was altered by TGF~31treatment in a concentration-dependent fashion. COX1 was increased by TGFß1, but only in astrocytes. TGFß1 increased COX2 expression in astrocytes and neurons. Thus, TGFß1 -induced increases in PGE2 concentration are regulated by COX. This study suggests that TGF/31 is an important regulator of immune and inflammatory processes in the CNS. Key Words: Cell culture-Cerebral cortex-Cytokine-Phospholipase A2-Prostaglandin. J. Neurochem. 71, 526-534 (1998).Prostaglandins, thromboxanes, and prostacyclin, collectively called prostanoids, are metabolites of arachidonic acid (AA). The initial step of prostanoid synthesis, the production of AA from fatty acids, is catalyzed by phospholipases, primarily phospholipase A2 (PLA2). AA is then converted to a prostanoid by cyclooxygenase (COX). There are at least two isoforms of COX: the constitutive COX1 and the inducible COX2.Prostanoids are commonly known as pivotal regulators of immune and inflammatory processes (Plescia and Racis, 1988). They are also present in the CNS, where they play important roles in the regulation of diverse CNS functions, i.e., cerebral blood flow, the sleep/wake cycle, and temperature regulation (Wolfe, 1982;Rothwell, 1992; Hayaishi, 1994). Although prostanoid concentrations are low in brain under normal conditions, they are increased in pathological states, such as ischemia, seizures, multiple sclerosis, acquired immunodeficiency syndrome, alcohol intoxication, and inflammation (Chen et al., 1986;George et al., 1986;Shimizu and Wolfe, 1990;Fretland, 1992;Griffin et al., 1994).Various growth factors, e.g., transforming growth factor ß (TGFß), have functions that parallel those of the prostanoids. Three isoforms of TGFß (TGF/31, TGF/32, and TGFß3...

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confidence: 55%

Section: Prostaglandin Synthesis By Cultured Astrocytes and Neuronsmentioning

confidence: 99%

Transforming Growth Factor β1 Regulates the Expression of Cyclooxygenase in Cultured Cortical Astrocytes and Neurons

Luo¹,

Lang²,

Miller

1998

Journal of Neurochemistry

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“…Our research group has previously reported the incorporation of curcumin into A2B star polymer micelles and effectiveness of this preparation in glioblastoma [63,64]. A retention of curcumin's biological activity in nanocarriers, an enhanced permeability and retention (EPR) effect and diffusion of curcumin into the neighboring glioblastoma cells could provide an improved therapeutic intervention in vivo [65] Pyrrolidine-2 is an inhibitor of cPLA2a, a key rate limiting enzyme in the synthesis of eicosanoids and a necessary player in the formation of lipid droplets [66,67]. In normal brain tissues, particularly in astrocytes and microglia, excessive PLA2 activation in response to stressors (e.g.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

Zhang

Cui

Amiri

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tIncreased lipid droplet number and fatty acid synthesis allow glioblastoma multiforme, the most common and aggressive type of brain cancer, to withstand accelerated metabolic rates and resist therapeutic treatments. Lipid droplets are postulated to sequester hydrophobic therapeutic agents, thereby reducing drug effectiveness. We hypothesized that the inhibition of lipid droplet accumulation in glioblastoma cells using pyrrolidine-2, a cytoplasmic phospholipase A2 alpha inhibitor, can sensitize cancer cells to the killing effect of curcumin, a promising anticancer agent isolated from the turmeric spice. We observed that curcumin localized in the lipid droplets of human U251N glioblastoma cells. Reduction of lipid droplet number using pyrrolidine-2 drastically enhanced the therapeutic effect of curcumin in both 2D and 3D glioblastoma cell models. The mode of cell death involved was found to be mediated by caspase-3. Comparatively, the current clinical chemotherapeutic standard, temozolomide, was significantly less effective in inducing glioblastoma cell death. Together, our results suggest that the inhibition of lipid droplet accumulation is an effective way to enhance the chemotherapeutic effect of curcumin against glioblastoma multiforme.

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“…It can be detected in the cytosolic fraction of the rat brain and human astrocytoma cell line, UC-11MG, using 1 -palmitoyl-2-14C] arachidonyl-sn-3-phosphocholine (Stephenson et al, 1994;Clemens et al, 1996). In human brain, cPLA 2 is found predominantly in astrocytes of the gray matter (Stephenson et al, 1994). No attempts have been made to purify and characterize this enzyme from brain tissue.…”

Section: Cpla2 In Brainmentioning

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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Calcium-sensitive cytosolic phospholipase A2 (cPLA2) is expressed in human brain astrocytes

Cited by 83 publications

References 56 publications

Transforming Growth Factor β1 Regulates the Expression of Cyclooxygenase in Cultured Cortical Astrocytes and Neurons

Transforming Growth Factor β1 Regulates the Expression of Cyclooxygenase in Cultured Cortical Astrocytes and Neurons

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

Phospholipase A₂ and Its Role in Brain Tissue

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Calcium-sensitive cytosolic phospholipase A2 (cPLA2) is expressed in human brain astrocytes

Cited by 83 publications

References 56 publications

Transforming Growth Factor β1 Regulates the Expression of Cyclooxygenase in Cultured Cortical Astrocytes and Neurons

Transforming Growth Factor β1 Regulates the Expression of Cyclooxygenase in Cultured Cortical Astrocytes and Neurons

Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma

Phospholipase A2 and Its Role in Brain Tissue

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Product

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Phospholipase A₂ and Its Role in Brain Tissue