Biochemical properties and pathophysiological roles of cytosolic phospholipase A2s

Kita, Yoshiaki; Ohto, Takayo; Uozumi, Naonori; Shimizu, Takao

doi:10.1016/j.bbalip.2006.08.001

Cited by 107 publications

(123 citation statements)

References 48 publications

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“…However, it cannot be ruled out that early increase in [Ca 2+ ] i levels also contribute to the toxic effects caused by TCDD. An early increase in [Ca 2+ ] i levels results in activation of phospholipase A2 with subsequent release of arachidonic acid (AA, n6 fatty acid) from membrane phospholipids (Kita et al 2006;Kinehara et al 2009;Kopec et al 2010). The released arachidonic acid acts as a substrate for COX-2 and cytochrome P450s and results in the production of pro-inflammatory eicosanoids (Bui et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Palaniswamy

Vishwanadha

Singaravelu

2014

Cell Stress and Chaperones

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Humans are systemically exposed to persistent organic pollutants, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has become a major environmental concern. Exposure to TCDD results in a wide variety of adverse health effects which is mediated by oxidative stress through CYP1A1 activation and arachidonic acid metabolites. Eicosapentaenoic acid (EPA) exhibits antioxidant property and competes with arachidonic acid in membrane phospholipids and produces anti-inflammatory EPA derivatives. Since both EPA and its derivatives have been reported to enhance the antioxidant mechanism, the present study aimed at studying whether EPA could offer protection against TCDDinduced oxidative stress and nephrotoxicity in Wistar rats. Estimation of kidney markers (serum urea and creatinine) and histopathological studies revealed that EPA treatment significantly reduced TCDD-induced renal damage. TCDDinduced oxidative damage was reflected in a significant increase in CYP1A1 activity and lipid peroxide levels with a concomitant decline in non-enzymic antioxidant (GSH) and various enzymic antioxidants such catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GPx). In addition, TCDD-induced oxidative stress also resulted in decline in Na + -K + and Mg 2+ATPases activities with increase in Ca 2+ ATPases activity. Oral treatment with EPA showed a significant cytoprotection against TCDD-induced renal oxidative stress by decreased CYP1A1 activity and enhanced antioxidant status. TCDD-induced alterations in ATPase enzyme activities were also prevented by EPA treatment. Our results show clear evidence that EPA ameliorates TCDD-induced oxidative stress and kidney damage; thus suggest the potential of EPA as an effective therapeutic agent against toxic effects mediated through redox imbalance.

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Section: Introductionmentioning

confidence: 99%

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Palaniswamy

Vishwanadha

Singaravelu

2014

Cell Stress and Chaperones

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“…cPLA 2 is of special interest since cPLA 2 α knockout mice show defects in inflammation and generation of eicosanoids [84][85]. cPLA 2 α −/− mice have fertility defects and are partially protected in models of brain injury.…”

Section: Cytosolic Phospholipase A2mentioning

confidence: 99%

Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma

Elsherbiny

Emara

Godbout

2013

Progress in Lipid Research

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Malignant gliomas are the most common adult brain cancers. In spite of aggressive treatment, recurrence occurs in the great majority of patients and is invariably fatal. Polyunsaturated fatty acids are abundant in brain, particularly ω-6 arachidonic acid (AA) and ω-3 docosahexaenoic acid (DHA). Although the levels of ω-6 and ω-3 polyunsaturated fatty acids are tightly regulated in brain, the ω-6:ω-3 ratio is dramatically increased in malignant glioma, suggesting deregulation of fundamental lipid homeostasis in brain tumor tissue. The migratory properties of malignant glioma cells can be modified by altering the ratio of AA:DHA in growth medium, with increased migration observed in AA-rich medium. This fatty acid-dependent effect on cell migration is dependent on expression of the brain fatty acid binding protein (FABP7) previously shown to bind DHA and AA. Increased levels of enzymes involved in eicosanoid production in FABP7-positive malignant glioma cells suggest that FABP7 is an important modulator of AA metabolism. We provide evidence that increased production of eicosanoids in FABP7-positive malignant glioma growing in an AA-rich environment contributes to tumor infiltration in the brain. We discuss pathways and molecules that may underlie FABP7/AA-mediated promotion of cell migration and FABP7/DHA-mediated inhibition of cell migration in malignant glioma.

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“…cPLA 2 α (group IVA) plays a pivotal role in providing AA because of its selectivity for phospholipds containing AA at the sn-2 position (4, 10). In group IV, cPLA 2 β (IVB), and cPLA 2 γ (IVC) require Ca 2+ for their activity, and newly identified isoforms of cPLA 2 including δ, ε, and ζ subtypes did not appear to have a preference for AA in phospholipids (10,11). So far, the Ca 2+ -independent PLA 2 (group VIA and VIB) family and some of the Group IV family show Ca 2+ -independent activity (12,13).…”

Section: Introductionmentioning

confidence: 99%

“…Secretory PLA 2 s require Ca 2+ at mM concentrations for their activity and contain an even number of cysteine residues at characteristic positions, each of which pairs with another specific cysteine to form a disulfide bridge, thus producing an adequate ternary structure (14). The PLA 2 enzymes and/ or release of AA are involved in various cellular functions including cell survival and growth (11,12,15,16). C1P triggered the translocation of cPLA 2 α from the cytosol to the perinuclear region in cells via interaction with its C2 domain and increased the enzyme activity (17,18).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Synthetic Sphingosine-1-Phosphate Analogs on Cytosolic Phospholipase A2α–Independent Release of Arachidonic Acid and Cell Toxicity in L929 Fibrosarcoma Cells: the Structure–Activity Relationship

et al. 2009

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Abstract. Sphingolipid metabolites including ceramide, sphingosine, and their phosphorylated products [sphingosine-1-phosphate (S1P) and ceramide-1-phosphate] regulate cell functions including arachidonic acid (AA) metabolism and cell death. The development of analogs of S1P may be useful for regulating these mediator-induced cellular responses. We synthesized new analogs of S1P and examined their effects on the release of AA and cell death in L929 mouse fibrosarcoma cells. Among the analogs tested, several compounds including DMB-mC11S [dimethyl (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate] and DMB-mC9S [dimethyl (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-3-(3'-nonyl)phenylpropyl phosphate] released AA within 1 h and caused cell death 6 h after treatment. The release of AA was observed in C12 cells [a L929 variant lacking a type α cytosolic phospholipase A 2 (cPLA 2 α)] and L929-cPLAα-siRNA cells (L929 cells treated with small interference RNA for cPLA 2 α). Treatment with pharmacological inhibitors of secretory and Ca 2+ -independent PLA 2 s decreased the DMB-mC11S-induced release of AA. The effect of the S1P analogs tested on the release of AA was comparable to that on cell death in L929 cells, and a high correlation coefficient was observed. Two analogs lacking a butoxycarbonyl moiety phenylpropyl phosphate] and DMAm-mC11S [dimethyl (2S,3R)-2-amino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate)] had inhibitory effects on the release of AA and cell toxicity induced by DMB-mC11S. Synthetic phosphorylated lipid analogs may be useful for studying PLA 2 activity and its toxicity in cells.[ Supplementary Fig. 1: available only at http://dx

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Biochemical properties and pathophysiological roles of cytosolic phospholipase A2s

Cited by 107 publications

References 48 publications

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma

Effects of Synthetic Sphingosine-1-Phosphate Analogs on Cytosolic Phospholipase A2α–Independent Release of Arachidonic Acid and Cell Toxicity in L929 Fibrosarcoma Cells: the Structure–Activity Relationship

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