Arachidonic acid as a neurotoxic and neurotrophic substance

Katsuki, Hiroshi; Okuda, Suguru

doi:10.1016/0301-0082(95)00016-o

Cited by 276 publications

(220 citation statements)

References 285 publications

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“…59 ROS formed by ArAc metabolism generate lipid peroxides and the cytotoxic byproducts malondialdehyde, 4-hydroxynonenal (HNE), 60 and acrolein, 61 , 62 which covalently bind to cellular proteins and alter their function. The time course of alterations in lipid metabolism and formation of lipid metabolites and lipid peroxidation products after transient cerebral ischemia is presented in Figure 3 .…”

Section: Reactive Oxygen Species and Lipid Peroxidationmentioning

confidence: 99%

Lipids and lipidomics in brain injury and diseases

Adibhatla

Hatcher

Dempsey

2006

AAPS J

147

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Lipidomics is systems-level analysis and characterization of lipids and their interacting moieties. The amount of information in the genomic and proteomic fi elds is greater than that in the lipidomics fi eld, because of the complex nature of lipids and the limitations of tools for analysis. The main innovation during recent years that has spurred advances in lipid analysis has been the development of new mass spectroscopic techniques, particularly the " soft ionization " techniques electrospray ionization and matrix-assisted laser desorption/ionization. Lipid metabolism may be of particular importance for the central nervous system, as it has a high concentration of lipids. The crucial role of lipids in cell signaling and tissue physiology is demonstrated by the many neurological disorders, including bipolar disorders and schizophrenia, and neurodegenerative diseases such as Alzheimer ' s, Parkinson ' s, and Niemann-Pick diseases, that involve deregulated lipid metabolism. Altered lipid metabolism is also believed to contribute to cerebral ischemic (stroke) injury. Lipidomics will provide a molecular signature to a certain pathway or a disease condition. Lipidomic analyses (characterizing complex mixtures of lipids and identifying previously unknown changes in lipid metabolism) together with RNA silencing, using small interfering RNA (siRNA), may provide powerful tools to elucidate the specifi c roles of lipid intermediates in cell signaling and open new opportunities for drug development.K e yw o r ds: Acrolein , arachidonic acid , cerebral ischemia , cytidine-5 ′ -diphosphocholine , CDP-choline , citicoline , docosahexaenoic acid , 4-hydroxynonenal , lipidomics , lipid peroxidation , MALDI-TOF , ESI-MS-MS , neuroprotectin D1 , 10,17S-docosatriene , phospholipases , phospholipids , RNA silencing , small interfering RNA , siRNA , reactive oxygen species , stroke INTRODUCTIONPhospholipids are important components of all mammalian cells and have a variety of biological functions: (1) they form lipid bilayers that provide structural integrity necessary for protein function, (2) they function as an energy reservoir (eg, triglycerides), and (3) they serve as precursors for various second messengers such as arachidonic acid, docosahexaenoic acid, ceramide, 1,2-diacylglycerol, phosphatidic acid, and lyso-phosphatidic acid. A deeper knowledge of the complexity of phospholipid metabolism will elevate our understanding of the role of lipids in maintaining normal cell physiology and how alterations in lipid metabolism contribute to various disease states. DEFINING A LIPIDLipids comprise an enormous number of chemically distinct molecules arising from combinations of fatty acids with various backbone structures. Indeed, it is diffi cult to defi ne what lipids are. Defi ning lipids as a class of biological molecules that share a high degree of solubility in organic solvents is considered at once too broad and too narrow, encompassing structurally and functionally unrelated molecules and excluding lipids, such as ganglioside...

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Section: Reactive Oxygen Species and Lipid Peroxidationmentioning

confidence: 99%

Lipids and lipidomics in brain injury and diseases

Adibhatla

Hatcher

Dempsey

2006

AAPS J

147

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“…Lysophospholipids may change membrane fluidity and permeability or be converted to bioactive molecules, such as plateletactivating factor (PAF) (Chao and Olson, 1993) and LPA (Moolenaar, 1995). Arachidonic acid has been implicated in both physiological (synaptic plasticity) and pathophysiological (neurodegeneration) processes (Katsuki and Okuda, 1995). For example, it modulates ion channels and regulates the activity of many enzyme proteins, such as protein kinase A, protein kinase C, NADPH oxidase, GTPase-activating protein, diacylglycerol kinase, Na~,K~-ATPase, and the platelet-derived growth factor receptor (Farooqui et al, 1997a).…”

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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“…Yehuda et al (2002) have shown that oxidative stress, which leads to an increase of free radicals increases lipid peroxidation and decreases the membrane fluidity (Yehuda et al, 2002). Enhanced free AA level by excessive activation of PLA 2 induced modification of membrane fluidity (Katsuki and Okuda, 1995), and it may exert several neurotoxic effects (Toborek et al, 1999;Garrido et al, 2001). In addition, arachidonic acid is a very potent messenger involved in synaptic transmission, and in a variety of signal transduction pathways (Katsuki and Okuda, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Enhanced free AA level by excessive activation of PLA 2 induced modification of membrane fluidity (Katsuki and Okuda, 1995), and it may exert several neurotoxic effects (Toborek et al, 1999;Garrido et al, 2001). In addition, arachidonic acid is a very potent messenger involved in synaptic transmission, and in a variety of signal transduction pathways (Katsuki and Okuda, 1995).…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol Transfer Protein Expression Altered by Aging and Parkinson Disease

Chalimoniuk

Snoek²,

Adamczyk

et al. 2006

Cell Mol Neurobiol

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SUMMARY1. Phosphatidylinositol transfer proteins (PI-TP) are responsible for the transport of phosphatidylinositol (PI) and other phospholipids from endoplasmic reticulum to the other membranes and indirectly for lipid mediated signaling. Till now little is known about PITPs in brain aging and neurodegeneration. The aim of this study was to investigate expression of PI-TP in the brain during aging and in animal's model of Parkinson disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Moreover, in vitro, effect of 1-methyl-4-phenyl-pyridine cation (MPP + ) on PI-TP, tyrosine hydroxylase (TH) protein level, and viability of cells was investigated.2. Wistar rats 4, 24, and 36 months old and C57/BL mice and rat pheochromocytoma (PC12) cell line were used for the studies. Mice C57/BL received three injections of MPTP in saline at 2 h intervals in a total dose of 40 mg/kg and then after 3, 7, and 14 days they were used for the investigation. PC12 cells were treated with increasing concentration (50-300 µM) of MPP + for 24 h at 37 • C. The level of PI-TP α and β and TH were determined using Western Blot analysis.3. Our data indicated that PI-TP α and β level decreased in brain of 36 months old rat by 20% comparing to the control value (4 months old). In animal's model of PD, PI-TP α and β level was significantly lower by 85, 69, 64% in striatum at 3, 7, and 14 days after MPTP injection, respectively, compared to the control value. MPP + decreased PI-TP α and β , TH expression, and viability of PC12 cells in a dose-dependent manner. H 2 O 2 , menadione, and NO donor significantly decreased the PI-TP level and viability of PC12 cells.4. Our results indicate the lower protein expression of PI-TP α and β in aged brain and in PD and suggest that oxidative stress may be responsible for the alteration of PI-TP.

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Arachidonic acid as a neurotoxic and neurotrophic substance

Cited by 276 publications

References 285 publications

Lipids and lipidomics in brain injury and diseases

Lipids and lipidomics in brain injury and diseases

Phospholipase A₂ and Its Role in Brain Tissue

Phosphatidylinositol Transfer Protein Expression Altered by Aging and Parkinson Disease

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Arachidonic acid as a neurotoxic and neurotrophic substance

Cited by 276 publications

References 285 publications

Lipids and lipidomics in brain injury and diseases

Lipids and lipidomics in brain injury and diseases

Phospholipase A2 and Its Role in Brain Tissue

Phosphatidylinositol Transfer Protein Expression Altered by Aging and Parkinson Disease

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Phospholipase A₂ and Its Role in Brain Tissue