phospholipases a2


Summary: Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.

Top Publications

  1. Polfus L, Gibbs R, Boerwinkle E. Coronary heart disease and genetic variants with low phospholipase A2 activity. N Engl J Med. 2015;372:295-6 pubmed publisher
  2. Yang H, Mosior M, Johnson C, Chen Y, Dennis E. Group-specific assays that distinguish between the four major types of mammalian phospholipase A2. Anal Biochem. 1999;269:278-88 pubmed
    ..Employing this system, we have found that iPLA2 is the dominant PLA2 in rat brain, and cPLA2 is the most abundant PLA2 in P388D1 macrophages and human amnionic WISH cells. ..
  3. El Mahdani N, Ameyar M, Cai Z, Colard O, Masliah J, Chouaib S. Resistance to TNF-induced cytotoxicity correlates with an abnormal cleavage of cytosolic phospholipase A2. J Immunol. 2000;165:6756-61 pubmed
    ..These findings suggest that the acquisition of cell resistance to this cytokine may involve an abnormal cPLA(2) cleavage. ..
  4. Atsumi G, Murakami M, Kojima K, Hadano A, Tajima M, Kudo I. Distinct roles of two intracellular phospholipase A2s in fatty acid release in the cell death pathway. Proteolytic fragment of type IVA cytosolic phospholipase A2alpha inhibits stimulus-induced arachidonate release, whereas that of type VI Ca2+-indep. J Biol Chem. 2000;275:18248-58 pubmed
  5. Zanassi P, Paolillo M, Schinelli S. Coexpression of phospholipase A2 isoforms in rat striatal astrocytes. Neurosci Lett. 1998;247:83-6 pubmed
    ..These data suggest that the two PLA2 isoforms expressed in striatal astrocytes might play different roles in cellular processes mediated by astrocytes. ..
  6. Costa L, Miles H, Diez R, Araujo C, Coni Molina C, Cervellino J. Phase I study of VRCTC-310, a purified phospholipase A2 purified from snake venom, in patients with refractory cancer: safety and pharmacokinetic data. Anticancer Drugs. 1997;8:829-34 pubmed
    ..Both cases had high VRCTC-310-specific IgG by EIA. MTD was 0.017 mg/kg and the recommended dose for phase II studies is 0.017 mg/kg. Stabilization was found in six patients. ..
  7. Faure G, Harvey A, Thomson E, Saliou B, Radvanyi F, Bon C. Comparison of crotoxin isoforms reveals that stability of the complex plays a major role in its pharmacological action. Eur J Biochem. 1993;214:491-6 pubmed
  8. Engmark M, Lomonte B, Gutierrez J, Laustsen A, De Masi F, Andersen M, et al. Cross-recognition of a pit viper (Crotalinae) polyspecific antivenom explored through high-density peptide microarray epitope mapping. PLoS Negl Trop Dis. 2017;11:e0005768 pubmed publisher
    ..This finding is likely to have large implications for the cross-reactivity of the antivenom and indicate that multiple different antibodies are likely to be needed for targeting an entire group of toxins in these recognized sites. ..
  9. Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992;258:607-14 pubmed
    ..Such prolonged activation of protein kinase C is essential for long-term cellular responses such as cell proliferation and differentiation. ..

More Information


  1. Pandey R, Ghorpade A. HIV-1 and alcohol abuse promote astrocyte inflammation: A mechanistic synergy via the cytosolic phospholipase A2 pathway. Cell Death Dis. 2015;6:e2017 pubmed publisher
  2. Zhang Y, Zhu W, Deng X, Peng J, Li C. Both non-covalent and covalent interactions were involved in the mechanism of detoxifying effects of persimmon tannin on Chinese cobra PLA2. Fitoterapia. 2017;120:41-51 pubmed publisher
  3. Atsumi G, Tajima M, Hadano A, Nakatani Y, Murakami M, Kudo I. Fas-induced arachidonic acid release is mediated by Ca2+-independent phospholipase A2 but not cytosolic phospholipase A2, which undergoes proteolytic inactivation. J Biol Chem. 1998;273:13870-7 pubmed
    ..Therefore, we conclude that iPLA2-mediated fatty acid release is facilitated in Fas-stimulated cells and plays a modifying although not essential role in the apoptotic cell death process. ..
  4. Zager R, Iwata M. Inorganic fluoride. Divergent effects on human proximal tubular cell viability. Am J Pathol. 1997;150:735-45 pubmed
    ..Reductions in cytosolic PLA2 activity could potentially contribute to this result. ..
  5. Davidson F, Dennis E. Evolutionary relationships and implications for the regulation of phospholipase A2 from snake venom to human secreted forms. J Mol Evol. 1990;31:228-38 pubmed
  6. Chen J, Cai H, Miao J, Xu X, Mao W. [Danlou Tablet Fought against Inflammatory Reaction in Atherosclerosis Rats with Intermingled Phlegm and Blood Stasis Syndrome and Its Mechanism Study]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2016;36:703-8 pubmed
    ..05), and those of LP-PLA2 and sPLA2 decreased in the high dose DT group (P < 0.01, P < 0.05). DT could fight against inflammatory reaction and AS possibly through inhibiting LP-PLA2 expression and reducing ox-LDL production. ..
  7. Sadeh M. Neurodegeneration associated with genetic defects in phospholipase A2. Neurology. 2009;73:819 pubmed publisher
  8. Chen X, Gresham A, Morrison A, Pentland A. Oxidative stress mediates synthesis of cytosolic phospholipase A2 after UVB injury. Biochim Biophys Acta. 1996;1299:23-33 pubmed
    ..The results indicate that UVB-induced upregulation of cPLA2 synthesis is mediated by UVB-induced formation of free radicals. ..
  9. Oliveira F, Noronha M, Lozano J. Biological and molecular properties of yellow venom of the Amazonian coral snake Micrurus surinamensis. Rev Soc Bras Med Trop. 2017;50:365-373 pubmed publisher
    ..These results indicate that antielapidic serum against M. surinamensis venom has weak potency (0.35mg/ml) in mice. ..
  10. Lokeshwari D, Achutha D, Srinivasan B, Shivalingegowda N, Krishnappagowda L, Kariyappa A. Synthesis of novel 2-pyrazoline analogues with potent anti-inflammatory effect mediated by inhibition of phospholipase A2: Crystallographic, in silico docking and QSAR analysis. Bioorg Med Chem Lett. 2017;27:3806-3811 pubmed publisher
    ..Thus, these compounds show promise for development as next-generation nonsteroidal anti-inflammatory drugs. ..
  11. Cavalcante W, Noronha Matos J, Timóteo M, Fontes M, Gallacci M, Correia de Sá P. Neuromuscular paralysis by the basic phospholipase A2 subunit of crotoxin from Crotalus durissus terrificus snake venom needs its acid chaperone to concurrently inhibit acetylcholine release and produce muscle blockage. Toxicol Appl Pharmacol. 2017;334:8-17 pubmed publisher
  12. Ross B, Moszczynska A, Erlich J, Kish S. Phospholipid-metabolizing enzymes in Alzheimer's disease: increased lysophospholipid acyltransferase activity and decreased phospholipase A2 activity. J Neurochem. 1998;70:786-93 pubmed
  13. Giurdanella G, Lazzara F, Caporarello N, Lupo G, Anfuso C, Eandi C, et al. Sulodexide prevents activation of the PLA2/COX-2/VEGF inflammatory pathway in human retinal endothelial cells by blocking the effect of AGE/RAGE. Biochem Pharmacol. 2017;142:145-154 pubmed publisher
    ..This mechanism, partially distinct from VEGF blockade, may contribute to the therapeutic effect of SDX. ..
  14. Shikano M, Masuzawa Y, Yazawa K, Takayama K, Kudo I, Inoue K. Complete discrimination of docosahexaenoate from arachidonate by 85 kDa cytosolic phospholipase A2 during the hydrolysis of diacyl- and alkenylacylglycerophosphoethanolamine. Biochim Biophys Acta. 1994;1212:211-6 pubmed
    ..The roles of DHA and cPLA2 in the synthesis of lipid mediators will be discussed in relation to the new aspects of the substrate specificity of cPLA2 provided here. ..
  15. Diez E, Chilton F, Stroup G, Mayer R, Winkler J, Fonteh A. Fatty acid and phospholipid selectivity of different phospholipase A2 enzymes studied by using a mammalian membrane as substrate. Biochem J. 1994;301 ( Pt 3):721-6 pubmed
  16. Singh P, Johnson J, Aklonis C, Bush K, Fisher S, O SULLIVAN J. Two new inhibitors of phospholipase A2 produced by Penicillium chermesinum. Taxonomy, fermentation, isolation, structure determination and biological properties. J Antibiot (Tokyo). 1985;38:706-12 pubmed
    ..89 microM and 12.8 microM, respectively. PLA2 preparations from Naja naja and Crotalus adamanteus were not significantly inhibited by plastatin and luteosporin. ..
  17. Basavarajappa B, Gowda T. Comparative characterization of two toxic phospholipases A2 from Indian cobra (Naja naja naja) venom. Toxicon. 1992;30:1227-38 pubmed
    ..The other PLA2, NN-XIb, in contrast has an i.p. LD50 of 0.22 mg/kg body weight, and it induces acute neurotoxicity. The NN-XIb-PLA2 is devoid of the other biological activities which are exhibited by NN-XIa-PLA2. ..
  18. Estevez A, O Regan M, Song D, Phillis J. Hyposmotically induced amino acid release from the rat cerebral cortex: role of phospholipases and protein kinases. Brain Res. 1999;844:1-9 pubmed
    ..The results show that although RVD may play a role, additional mechanisms, including phospholipase activation, must be involved in the ischemia-evoked release of excitotoxic amino acids. ..
  19. Gresham A, Masferrer J, Chen X, Leal Khouri S, Pentland A. Increased synthesis of high-molecular-weight cPLA2 mediates early UV-induced PGE2 in human skin. Am J Physiol. 1996;270:C1037-50 pubmed
    ..These results suggest that increased cPLA2 synthesis occurs only when skin is exposed to UV doses that are sufficient to cause erythema and indicate expression of cPLA2 participates in acute UV inflammation. ..
  20. Talbot K, Young R, Jolly Tornetta C, Lee V, Trojanowski J, Wolf B. A frontal variant of Alzheimer's disease exhibits decreased calcium-independent phospholipase A2 activity in the prefrontal cortex. Neurochem Int. 2000;37:17-31 pubmed
    ..That could cause an early elevation of prefrontal free fatty acids, which can stimulate polymerization of tau and thus promote the prefrontal neurofibrillary tangle formation characteristic of frontal AD. ..
  21. Almeida T, Cunha R, Ribeiro J. Facilitation by arachidonic acid of acetylcholine release from the rat hippocampus. Brain Res. 1999;826:104-11 pubmed
  22. Wolf M, Gross R. The calcium-dependent association and functional coupling of calmodulin with myocardial phospholipase A2. Implications for cardiac cycle-dependent alterations in phospholipolysis. J Biol Chem. 1996;271:20989-92 pubmed
  23. Uyama T, Tsuboi K, Ueda N. An involvement of phospholipase A/acyltransferase family proteins in peroxisome regulation and plasmalogen metabolism. FEBS Lett. 2017;591:2745-2760 pubmed publisher
    ..In this article, we will review our recent findings about PLAAT proteins, with special reference to their roles in peroxisome biogenesis and plasmalogen metabolism. ..
  24. Berenbaum F, Thomas G, Poiraudeau S, Bereziat G, Corvol M, Masliah J. Insulin-like growth factors counteract the effect of interleukin 1 beta on type II phospholipase A2 expression and arachidonic acid release by rabbit articular chondrocytes. FEBS Lett. 1994;340:51-5 pubmed
    ..They may therefore be considered as potential antiinflammatory agents. ..
  25. Ganz T, Weiss J. Antimicrobial peptides of phagocytes and epithelia. Semin Hematol. 1997;34:343-54 pubmed
    ..Such antimicrobial substances are of interest not only for students of phagocytic and epithelial host defenses but may lead to the development of novel pharmaceuticals for the treatment of infections and their sequellae. ..
  26. Weichenberger C, Pozharski E, Rupp B. Twilight reloaded: the peptide experience. Acta Crystallogr D Struct Biol. 2017;73:211-222 pubmed publisher
  27. Lippestad M, Hodges R, Utheim T, Serhan C, Dartt D. Resolvin D1 Increases Mucin Secretion in Cultured Rat Conjunctival Goblet Cells via Multiple Signaling Pathways. Invest Ophthalmol Vis Sci. 2017;58:4530-4544 pubmed publisher
  28. Shu S, Xu Y, Xie L, Ouyang Y. The role of C/EBP? phosphorylation in modulating membrane phospholipids repairing in LPS-induced human lung/bronchial epithelial cells. Gene. 2017;629:76-85 pubmed publisher
    ..The significance of this study lies in that artificial C/EBP ? phosphorylation regulation may ease the membrane damage in ALI and improve membrane repair. ..
  29. Stephenson D, Rash K, Smalstig B, Roberts E, Johnstone E, Sharp J, et al. Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration. Glia. 1999;27:110-28 pubmed
    ..These results suggest that cytosolic phospholipase A(2) may prove an attractive therapeutic target for neurodegeneration. ..
  30. Murakami M, Nakatani Y, Atsumi G, Inoue K, Kudo I. Regulatory functions of phospholipase A2. Crit Rev Immunol. 1997;17:225-83 pubmed
    ..In particular, the roles of type II sPLA2 and cPLA2 in lipid mediator generation are discussed. ..
  31. Stephenson D, Lemere C, Selkoe D, Clemens J. Cytosolic phospholipase A2 (cPLA2) immunoreactivity is elevated in Alzheimer's disease brain. Neurobiol Dis. 1996;3:51-63 pubmed
    ..The finding of elevated levels of cPLA2 immunoreactivity in AD brain supports the hypothesis that there is an active inflammatory process occurring in AD. ..
  32. Wissing D, Mouritzen H, Egeblad M, Poirier G, Jaattela M. Involvement of caspase-dependent activation of cytosolic phospholipase A2 in tumor necrosis factor-induced apoptosis. Proc Natl Acad Sci U S A. 1997;94:5073-7 pubmed
    ..Thus, our results suggest a novel caspase-dependent activation pathway for cPLA2 during apoptosis and identify cPLA2 as a mediator of TNF-induced cell death acting downstream of caspases. ..
  33. Kramer R, Roberts E, Manetta J, Putnam J. The Ca2(+)-sensitive cytosolic phospholipase A2 is a 100-kDa protein in human monoblast U937 cells. J Biol Chem. 1991;266:5268-72 pubmed
  34. Woo C, Eom Y, Yoo M, You H, Han H, Song W, et al. Tumor necrosis factor-alpha generates reactive oxygen species via a cytosolic phospholipase A2-linked cascade. J Biol Chem. 2000;275:32357-62 pubmed
    ..Our findings suggest that LTB(4) production by 5-LO is situated downstream of the Rac-cPLA(2) cascade, and we conclude that Rac, cPLA(2), and LTB(4) play pivotal roles in the ROS-generating cascade triggered by TNF-alpha. ..
  35. Ponce Soto L, Leiva L, Landucci E. Understanding the molecular mechanism and structure-function relationship of the toxicity of PLA2 and K49 homologs in snake venom. Biomed Res Int. 2013;2013:243047 pubmed publisher
  36. Vulfius C, Kasheverov I, Kryukova E, Spirova E, Shelukhina I, Starkov V, et al. Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors. PLoS ONE. 2017;12:e0186206 pubmed publisher
    b>Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes...
  37. Vieira S, Da Rocha S, Neves Ferreira A, Almeida R, Perales J. Heterologous expression of the antimyotoxic protein DM64 in Pichia pastoris. PLoS Negl Trop Dis. 2017;11:e0005829 pubmed publisher
    ..rDM64 formed a noncovalent complex with myotoxin II (Lys49-PLA2) from Bothrops asper and displayed biological activity that was similar to that of native DM64, inhibiting the cytotoxicity of myotoxin II by 92% at a 1:1 molar ratio. ..
  38. Pruzanski W, Greenwald R, Street I, Laliberte F, Stefanski E, Vadas P. Inhibition of enzymatic activity of phospholipases A2 by minocycline and doxycycline. Biochem Pharmacol. 1992;44:1165-70 pubmed
    Extracellular phospholipases A2 play an important role in articular and extra-articular inflammatory processes...
  39. Dennis E, Cao J, Hsu Y, Magrioti V, Kokotos G. Phospholipase A2 enzymes: physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention. Chem Rev. 2011;111:6130-85 pubmed publisher
  40. Georgieva D, Hildebrand D, Simas R, Coronado M, Kwiatkowski M, Schluter H, et al. Protein Profile Analysis of Two Australian Snake Venoms by One- Dimensional Gel Electrophoresis and MS/MS Experiments. Curr Med Chem. 2017;24:1892-1908 pubmed publisher
    ..pharmacologically active components, which were assigned to the following protein families: basic and acidic phospholipases A2 (PLA2s), L-amino acid oxidases (LAAOs), P-III metalloproteinases (P-III SVMPs), 5'- nucleotidases (5'-NTDs), ..
  41. Lehtonen J, Holopainen J, Kinnunen P. Activation of phospholipase A2 by amyloid beta-peptides in vitro. Biochemistry. 1996;35:9407-14 pubmed
  42. Khan M, Nahar N, Rashid R, Chowdhury A, Rashid M. Computational investigations of physicochemical, pharmacokinetic, toxicological properties and molecular docking of betulinic acid, a constituent of Corypha taliera (Roxb.) with Phospholipase A2 (PLA2). BMC Complement Altern Med. 2018;18:48 pubmed publisher
    ..89 kJ/mol). Our computed properties may assist the development of analytical method to assay BA or to develop BA derivatives with better pharmacokinetic and toxicological profile. ..
  43. Jang K, Lee Z, Kim B, Jung Y, Han H, Kim M, et al. Identification and characterization of Vibrio vulnificus plpA encoding a phospholipase A2 essential for pathogenesis. J Biol Chem. 2017;292:17129-17143 pubmed publisher
    ..Taken together, this study demonstrated that VvPlpA is a type II secretion system-dependent secretory phospholipase A2 regulated by HlyU and CRP and is essential for the pathogenicity of V. vulnificus. ..
  44. Lim K, Rice G, De Groot C, Taylor R. Plasma type II phospholipase A2 levels are elevated in severe preeclampsia. Am J Obstet Gynecol. 1995;172:998-1002 pubmed
    ..Plasma from preeclamptic women increased secretion of prostacyclin, but not type II phospholipase A2 by endothelial cells in culture. ..
  45. Wolf M, Wang J, Turk J, Gross R. Depletion of intracellular calcium stores activates smooth muscle cell calcium-independent phospholipase A2. A novel mechanism underlying arachidonic acid mobilization. J Biol Chem. 1997;272:1522-6 pubmed
    ..Collectively, these results identify a novel paradigm which links alterations in calcium homeostasis to the calmodulin-mediated regulation of calcium-independent phospholipase A2 through the depletion of internal calcium stores. ..
  46. Prabhudeva M, Bharath S, Kumar A, Naveen S, Lokanath N, Mylarappa B, et al. Design and environmentally benign synthesis of novel thiophene appended pyrazole analogues as anti-inflammatory and radical scavenging agents: Crystallographic, in silico modeling, docking and SAR characterization. Bioorg Chem. 2017;73:109-120 pubmed publisher