{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:48:11Z","timestamp":1790826491040,"version":"4.1.0"},"reference-count":87,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010699","name":"Monash University Malaysia","doi-asserted-by":"publisher","award":["GA-HW-18-L02"],"award-info":[{"award-number":["GA-HW-18-L02"]}],"id":[{"id":"10.13039\/501100010699","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Higher Education Malaysia","award":["FRGS19-040-0648"],"award-info":[{"award-number":["FRGS19-040-0648"]}]},{"name":"Australian National Health and Medical Research Council (NHMRC)","award":["1110343"],"award-info":[{"award-number":["1110343"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Phospholipase A2 (PLA2) toxins are one of the main toxin families found in snake venom. PLA2 toxins are associated with various detrimental effects, including neurotoxicity, myotoxicity, hemostatic disturbances, nephrotoxicity, edema, and inflammation. Although Naja sumatrana venom contains substantial quantities of PLA2 components, there is limited information on the function and activities of PLA2 toxins from the venom. In this study, a secretory PLA2 from the venom of Malaysian N. sumatrana, subsequently named A2-EPTX-Nsm1a, was isolated, purified, and characterized. A2-EPTX-Nsm1a was purified using a mass spectrometry-guided approach and multiple chromatography steps. Based on LC-MSMS, A2-EPTX-Nsm1a was found to show high sequence similarity with PLA2 from venoms of other Naja species. The PLA2 activity of A2-EPTX-Nsm1 was inhibited by 4-BPB and EDTA. A2-EPTX-Nsm1a was significantly less cytotoxic in a neuroblastoma cell line (SH-SY5Y) compared to crude venom and did not show a concentration-dependent cytotoxic activity. To our knowledge, this is the first study that characterizes and investigates the cytotoxicity of an Asp49 PLA2 isolated from Malaysian N. sumatrana venom in a human neuroblastoma cell line.<\/jats:p>","DOI":"10.3390\/toxins13120859","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T02:48:13Z","timestamp":1638845293000},"page":"859","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Isolation and Characterization of A2-EPTX-Nsm1a, a Secretory Phospholipase A2 from Malaysian Spitting Cobra (Naja sumatrana) Venom"],"prefix":"10.3390","volume":"13","author":[{"given":"Nur Atiqah Haizum","family":"Abdullah","sequence":"first","affiliation":[{"name":"Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya 47500, Malaysia"},{"name":"Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0327-060X","authenticated-orcid":false,"given":"Muhamad Rusdi Ahmad","family":"Rusmili","sequence":"additional","affiliation":[{"name":"Kulliyyah of Pharmacy, Kuantan Campus, International Islamic University Malaysia, Bandar Indera Mahkota, Kuantan 25200, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syafiq Asnawi","family":"Zainal Abidin","sequence":"additional","affiliation":[{"name":"Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya 47500, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9865-6224","authenticated-orcid":false,"given":"Mohd Farooq","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya 47500, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9919-0144","authenticated-orcid":false,"given":"Wayne C.","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Monash Venom Group, Department of Pharmacology, Biomedical Discovery Institute, Monash University, Clayton, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9225-3678","authenticated-orcid":false,"given":"Iekhsan","family":"Othman","sequence":"additional","affiliation":[{"name":"Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Subang Jaya 47500, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"ref_1","unstructured":"Das, I. (2015). Field Guide to the Reptiles of South-East Asia, Bloomsbury Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Stuebing, R.B., Inger, R.F., and Tan, F.L. (1999). Field Guide to the Snakes of Borneo, Natural History Publications (Borneo).","DOI":"10.2307\/1447418"},{"key":"ref_3","unstructured":"WHO (2016). Guidelines for the Management of Snake Bites, Regional office for South-East Asia, World Health Organization."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-94-007-6386-9_54","article-title":"Snakebite and envenomation management in Malaysia","volume":"2","author":"Ismail","year":"2015","journal-title":"Clin. Toxicol Asia Pac. Afr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.actatropica.2014.01.014","article-title":"Proteomic characterization of venom of the medically important Southeast Asian Naja sumatrana (Equatorial spitting cobra)","volume":"133","author":"Yap","year":"2014","journal-title":"Acta Trop."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1074\/mcp.M700094-MCP200","article-title":"Evolution of an Arsenal: Structural and functional diversification of the venom system in the advanced snakes (Caenophidia)","volume":"7","author":"Fry","year":"2008","journal-title":"Mol. Cell. Proteom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12795","DOI":"10.1021\/bi701304e","article-title":"Restoration of enzymatic activity in a Ser-49 phospholipase A2 homologue decreases its Ca2+-independent membrane-damaging activity and increases its toxicity","volume":"46","author":"Petan","year":"2007","journal-title":"Biochemistry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.toxicon.2009.05.003","article-title":"Island specific expression of a novel [Lys49] phospholipase A2 (BPIII) in Protobothrops flavoviridis venom in Amami\u2013Oshima, Japan","volume":"54","author":"Murakami","year":"2009","journal-title":"Toxicon"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.toxicon.2017.01.002","article-title":"Exploring and understanding the functional role, and biochemical and structural characteristics of an acidic phospholipase A2, AplTx-I, purified from Agkistrodon piscivorus leucostoma snake venom","volume":"127","author":"Resende","year":"2017","journal-title":"Toxicon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/j.ijbiomac.2018.09.053","article-title":"Antitumor potential of Pllans\u2013II, an acidic Asp49\u2013PLA2 from Porthidium lansbergii lansbergii snake venom on human cervical carcinoma HeLa cells","volume":"122","author":"Lopes","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.toxicon.2013.06.013","article-title":"Structural and functional studies with mytoxin II from Bothrops moojeni reveal remarkable similarities and differences compared to other catalytically inactive phospholipases A2-like","volume":"72","author":"Salvador","year":"2013","journal-title":"Toxicon"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1016\/j.toxicon.2012.08.019","article-title":"Isolation, amino acid sequence and biological characterization of an \u201caspartic-49\u201d phospholipase A2 from Bothrops (Rhinocerophis) ammodytoides venom","volume":"60","author":"Clement","year":"2012","journal-title":"Toxicon"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.toxicon.2011.11.007","article-title":"Synergism between baltergin metalloproteinase and Ba SPII RP4 PLA2 from Bothrops alternatus venom on skeletal muscle (C2C12) cells","volume":"59","author":"Bustillo","year":"2012","journal-title":"Toxicon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ijbiomac.2012.05.006","article-title":"Crystallographic portrayal of different conformational states of a Lys49 phospholipase A2 homologue: Insights into structural determinants for myotoxicity and dimeric configuration","volume":"51","author":"Ullah","year":"2012","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.cbpc.2011.03.013","article-title":"Biochemical and pharmacological characterization of PhTX-I a new myotoxic phospholipase A2 isolated from Porthidium hyoprora snake venom","volume":"154","author":"Marangoni","year":"2011","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.toxicon.2009.01.021","article-title":"Biochemical and biological characterization of a PLA2 from crotoxin complex of Crotalus durissus cumanensis","volume":"53","author":"Marangoni","year":"2009","journal-title":"Toxicon"},{"key":"ref_17","first-page":"78","article-title":"Novel acidic phospholipase A2 from Porthidium hyoprora causes inflammation with mast cell rich infiltrate","volume":"1","author":"Marques","year":"2015","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.cbpc.2011.06.003","article-title":"Isolation and functional characterization of proinflammatory acidic phospholipase A2 from Bothrops leucurus snake venom","volume":"154","author":"Nunes","year":"2011","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.toxicon.2011.02.024","article-title":"Umbelliferone induces changes in the structure and pharmacological activities of Bn IV, a phospholipase A2 isoform isolated from Bothrops neuwiedi","volume":"57","author":"Toyama","year":"2011","journal-title":"Toxicon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.toxicon.2009.12.016","article-title":"Induction of microvascular leakage and histamine release by promutoxin, an Arg49 phospholipase A2","volume":"55","author":"Wei","year":"2010","journal-title":"Toxicon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.toxicon.2008.12.018","article-title":"Effect of umbelliferone (7-hydroxycoumarin, 7-HOC) on the enzymatic, edematogenic and necrotic activities of secretory phospholipase A2 (sPLA2) isolated from Crotalus durissus collilineatus venom","volume":"53","author":"Toyama","year":"2009","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2014.01.008","article-title":"Neurotoxicity of coral snake phospholipases A2 in cultured rat hippocampal neurons","volume":"1552","author":"Garcia","year":"2014","journal-title":"Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jprot.2014.02.027","article-title":"Eastern coral snake Micrurus fulvius venom toxicity in mice is mainly determined by neurotoxic phospholipases A2","volume":"105","author":"Vergara","year":"2014","journal-title":"J. Proteom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.toxicon.2014.04.008","article-title":"Crotoxin from Crotalus durissus terrificus snake venom induces the release of glutamate from cerebrocortical synaptosomes via N and P\/Q calcium channels","volume":"85","author":"Lomeo","year":"2014","journal-title":"Toxicon"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.bcp.2010.03.030","article-title":"Characterisation of the heterotrimeric presynaptic phospholipase A2 neurotoxin complex from the venom of the common death adder (Acanthophis antarcticus)","volume":"80","author":"Blacklow","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.toxicon.2020.06.007","article-title":"Bothrops leucurus venom induces acute hypotension in rats by means of its phospholipase A2 (blD-PLA2)","volume":"185","author":"Menezes","year":"2020","journal-title":"Toxicon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1016\/j.febslet.2014.10.032","article-title":"Crystal structure of phospholipase PA2-Vb, a protease-activated receptor agonist from the Trimeresurus stejnegeri snake venom","volume":"588","author":"Zeng","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.toxicon.2013.10.001","article-title":"Mechanism of in vivo anticoagulant and haemolytic activity by a neutral phospholipase A2 purified from Daboia russelii russelii venom: Correlation with clinical manifestations in Russell\u2019s Viper envenomed patients","volume":"76","author":"Saikia","year":"2013","journal-title":"Toxicon"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.toxicon.2020.12.004","article-title":"Bothrops pauloensis snake venom-derived Asp-49 and Lys-49 phospholipases A2 mediates acute kidney injury by oxidative stress and release of inflammatory cytokines","volume":"190","author":"Marinho","year":"2021","journal-title":"Toxicon"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ijbiomac.2019.05.164","article-title":"Antitumor and antimetastatic effects of PLA2-BthTX-II from Bothrops jararacussu venom on human breast cancer cells","volume":"135","author":"Lopes","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ijbiomac.2018.06.082","article-title":"Genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) homologue from Bothrops pauloensis snake venom, on MDA-MB-231 breast cancer cells","volume":"118","author":"Silva","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ijbiomac.2015.10.080","article-title":"Human breast cancer cell death induced by BnSP-6, a Lys-49 PLA2 homologue from Bothrops pauloensis venom","volume":"82","author":"Azevedo","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.matbio.2009.03.007","article-title":"MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom, inhibits tumor cells adhesion and migration","volume":"28","author":"Bazaa","year":"2009","journal-title":"Matrix Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.toxicon.2009.01.003","article-title":"Two purified and characterized phospholipases A2 from Cerastes cerastes venom, that inhibit cancerous cell adhesion and migration","volume":"53","author":"Luis","year":"2009","journal-title":"Toxicon"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.toxlet.2008.12.004","article-title":"Catalytic activity-independent pathway is involved in phospholipase A2-induced apoptotic death of human leukemia U937 cells via Ca2+-mediated p38 MAPK activation and mitochondrial depolarization","volume":"185","author":"Liu","year":"2009","journal-title":"Toxicol. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105099","DOI":"10.1016\/j.tiv.2021.105099","article-title":"Antiangiogenic effects of phospholipase A2 Lys49 BnSP-7 from Bothrops pauloensis snake venom on endothelial cells: An in vitro and ex vivo approach","volume":"72","author":"Polloni","year":"2021","journal-title":"Toxicol. Vitr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.toxicon.2021.03.015","article-title":"Understanding the mechanism of action of peptide (p-BthTX-I)2 derived from C-terminal region of phospholipase A2 (PLA2)-like bothropstoxin-I on Gram-positive and Gram-negative bacteria","volume":"196","author":"Piccoli","year":"2021","journal-title":"Toxicon"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.toxicon.2008.10.021","article-title":"Enzymatic and structural characterization of new PLA2 isoform isolated from white venom of Crotalus durissus ruruima","volume":"53","author":"Marangoni","year":"2009","journal-title":"Toxicon"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.intimp.2016.04.025","article-title":"Liposomes containing an ASP49-phospholipase A2 from Bothrops jararacussu snake venom as experimental therapy against cutaneous leishmaniasis","volume":"36","author":"Macedo","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.toxicon.2012.06.010","article-title":"LmrTX, a basic PLA2 (D49) purified from Lachesis muta rhombeata snake venom with enzymatic-related antithrombotic and anticoagulant activity","volume":"60","author":"Damico","year":"2012","journal-title":"Toxicon"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.toxicon.2011.02.018","article-title":"An acidic phospholipase A2 (RVVA-PLA2-I) purified from Daboia russelli venom exerts its anticoagulant activity by enzymatic hydrolysis of plasma phospholipids and by non-enzymatic inhibition of factor Xa in a phospholipids\/Ca2+ independent manner","volume":"57","author":"Saikia","year":"2011","journal-title":"Toxicon"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.toxicon.2011.05.021","article-title":"Crotoxin and phospholipases A2 from Crotalus durissus terrificus showed antiviral activity against dengue and yellow fever viruses","volume":"59","author":"Muller","year":"2012","journal-title":"Toxicon"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.toxicon.2010.12.021","article-title":"A phospholipase A2 isolated from Lachesis muta snake venom increases the survival of retinal ganglion cells in vitro","volume":"57","author":"Fuly","year":"2011","journal-title":"Toxicon"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.toxicon.2009.05.010","article-title":"Purification, characterization, and cDNA cloning of acidic platelet aggregation inhibiting phospholipases A2 from the snake venom of Vipera lebetina (Levantine viper)","volume":"54","author":"Vija","year":"2009","journal-title":"Toxicon"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1042\/BST20200110","article-title":"Cytotoxicity of snake venom enzymatic toxins: Phospholipase A2 and l-amino acid oxidase","volume":"48","author":"Hiu","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0041-0101(96)00071-2","article-title":"Cloning and characterization of cDNAs encoding three isoforms of phospholipase A2 in Malayan spitting cobra (Naja naja sputatrix) venom","volume":"35","author":"Armugam","year":"1997","journal-title":"Toxicon"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1093\/oxfordjournals.molbev.a026382","article-title":"Structure and phylogeny of the venom group I phospholipase A2 gene","volume":"17","author":"Jeyaseelan","year":"2000","journal-title":"Mol. Biol. Evol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1006\/abbi.1996.0137","article-title":"Phospholipase A2 from Naja naja sputatrix venom is a muscarinic acetylcholine receptor inhibitor","volume":"328","author":"Miyoshi","year":"1996","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.toxicon.2008.05.020","article-title":"A rational nomenclature for naming peptide toxins from spiders and other venomous animals","volume":"52","author":"King","year":"2008","journal-title":"Toxicon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.toxicon.2012.05.020","article-title":"Development of a rational nomenclature for naming peptide and protein toxins from sea anemones","volume":"60","author":"Oliveira","year":"2012","journal-title":"Toxicon"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e3142","DOI":"10.7717\/peerj.3142","article-title":"Comparative venom gland transcriptomics of Naja kaouthia (monocled cobra) from Malaysia and Thailand: Elucidating geographical venom variation and insights into sequence novelty","volume":"5","author":"Tan","year":"2017","journal-title":"PeerJ"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Chong, H.P., Tan, K.Y., Tan, N.H., and Tan, C.H. (2019). Exploring the Diversity and Novelty of Toxin Genes in Naja sumatrana, the Equatorial Spitting Cobra from Malaysia through De Novo Venom-Gland Transcriptomics. Toxins, 11.","DOI":"10.3390\/toxins11020104"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1126\/science.abb9303","article-title":"Convergent evolution of pain-inducing defensive venom components in spitting cobras","volume":"371","author":"Kazandjian","year":"2021","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Serino-Silva, C., Morais-Zani, K., Hikari Toyama, M., Toyama, D.O., Gaeta, H.H., Rodrigues, C.F.B., Aguiar, W.D.S., Tashima, A.K., Grego, K.F., and Tanaka-Azevedo, A.M. (2018). Purification and characterization of the first \u03b3-phospholipase inhibitor (\u03b3PLI) from Bothrops jararaca snake serum. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193105"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.ijbiomac.2019.09.032","article-title":"Local and systemic effects of BtaMP-1, a new weakly hemorrhagic snake venom metalloproteinase purified from Bothriopsis taeniata Snake Venom","volume":"141","author":"Marunak","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.biochi.2019.03.022","article-title":"Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom","volume":"162","author":"Delgadillo","year":"2019","journal-title":"Biochimie"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"104809","DOI":"10.1016\/j.tiv.2020.104809","article-title":"Disintegrins extracted from totonacan rattlesnake (Crotalus totonacus) venom and their anti-adhesive and anti-migration effects on MDA-MB-231 and HMEC-1 cells","volume":"65","year":"2020","journal-title":"Toxicol. Vitr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"13057","DOI":"10.1016\/S0021-9258(17)36794-7","article-title":"Diversity of group types, regulation, and function of phospholipase A2","volume":"269","author":"Dennis","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6130","DOI":"10.1021\/cr200085w","article-title":"Phospholipase A2 enzymes: Physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention","volume":"111","author":"Dennis","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jbior.2017.10.009","article-title":"Review of four major distinct types of human phospholipase A2","volume":"67","author":"Vasquez","year":"2018","journal-title":"Adv. Biol. Regul."},{"key":"ref_61","first-page":"S177","article-title":"Phospholipase Superfamily: Structure, Functions, and Biotechnological Applications","volume":"85","author":"Filkin","year":"2020","journal-title":"Biochemistry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.toxicon.2003.11.004","article-title":"Chemical modifications of phospholipases A2 from snake venoms: Effects on catalytic and pharmacological properties","volume":"42","author":"Soares","year":"2003","journal-title":"Toxicon"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0090-6980(02)00020-5","article-title":"Phospholipase A2 enzymes","volume":"68\u201369","author":"Kudo","year":"2002","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_64","first-page":"612649","article-title":"Biochemical, pharmacological, and structural characterization of new basic PLA2 Bbil-TX from Bothriopsis bilineata snake venom","volume":"2013","author":"Winck","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/jcb.240390404","article-title":"The role of Asp-49 and other conserved amino acids in phospholipases A2 and their importance for enzymatic activity","volume":"39","author":"Slotboom","year":"1989","journal-title":"J. Cell. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5768","DOI":"10.1016\/S0021-9258(18)83616-X","article-title":"Structure and properties of a human non-pancreatic phospholipase A2","volume":"264","author":"Kramer","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/0006-291X(92)91270-Z","article-title":"Interaction mode of n-dodecylphosphorylcholine, a substrate analogue, with bovine pancreas phospholipase A2 as determined by X-ray crystal analysis","volume":"187","author":"Tomoo","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Yap, M.K., Tan, N.H., Sim, S.M., Fung, S.Y., and Tan, C.H. (2014). Pharmacokinetics of Naja sumatrana (equatorial spitting cobra) venom and its major toxins in experimentally envenomed rabbits. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002890"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1016\/0006-2952(90)90717-Y","article-title":"Inhibitory effect of EDTA \u00b7 Ca2+ on the hydrolysis of synaptosomal phospholipids by phospholipase A2 toxins and enzymes","volume":"40","author":"Shina","year":"1990","journal-title":"Biochem. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.3390\/toxins6113077","article-title":"PhTX-II a basic myotoxic phospholipase A2 from Porthidium hyoprora snake venom, pharmacological characterization and amino acid sequence by mass spectrometry","volume":"6","author":"Marangoni","year":"2014","journal-title":"Toxins"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.bcp.2014.07.001","article-title":"Isolation and characterization of a presynaptic neurotoxin, P-elapitoxin-Bf1a from Malaysian Bungarus fasciatus venom","volume":"91","author":"Rusmili","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/S0041-0101(99)00208-1","article-title":"Myotoxic activity of an acidic phospholipase A2 isolated from Lachesis muta (Bushmaster) snake venom","volume":"38","author":"Fuly","year":"2000","journal-title":"Toxicon"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13024-017-0149-0","article-title":"The SH-SY5Y cell line in Parkinson\u2019s disease research: A systematic review","volume":"12","author":"Xicoy","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/978-1-62703-640-5_2","article-title":"Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology","volume":"1078","author":"Kovalevich","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_75","first-page":"741","article-title":"Coordinate morphological and biochemical interconversion of human neuroblastoma cells","volume":"71","author":"Ross","year":"1983","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neulet.2012.07.057","article-title":"Protective effects of 27- and 24-hydroxycholesterol against staurosporine-induced cell death in undifferentiated neuroblastoma SH-SY5Y cells","volume":"525","author":"Emanuelsson","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.3233\/JAD-161086","article-title":"Phytochemical Ginkgolide B attenuates amyloid-\u03b21-42 induced oxidative damage and altered cellular responses in human neuroblastoma SH-SY5Y cells","volume":"60","author":"Gill","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neuropharm.2014.03.019","article-title":"Neuroprotective effects of metabotropic glutamate receptor group II and III activators against MPP+-induced cell death in human neuroblastoma SH-SY5Y cells: The impact of cell differentiation state","volume":"83","author":"Jantas","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.npep.2018.04.009","article-title":"PACAP and VIP regulate hypoxia-inducible factors in neuroblastoma cells exposed to hypoxia","volume":"69","author":"Maugeri","year":"2018","journal-title":"Neuropeptides"},{"key":"ref_80","first-page":"53193","article-title":"Differentiation of the SH-SY5Y human neuroblastoma cell line","volume":"108","author":"Shipley","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s00702-021-02331-1","article-title":"SIRT1 and SIRT2 modulators reduce LPS-induced inflammation in HAPI microglial cells and protect SH-SY5Y neuronal cells in vitro","volume":"128","author":"Zhang","year":"2021","journal-title":"J. Neural Transm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"105879","DOI":"10.1155\/2014\/105879","article-title":"An Asp49 phospholipase A2 snake venom induces cyclooxygenase-2 expression and prostaglandin E2 production via activation of NF-\u03baB, p38MAPK, and PKC in macrophages","volume":"2014","author":"Moreira","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Bazaa, A., Pasquier, E., Defilles, C., Limam, I., Kessentini-Zouari, R., Kallech-Ziri, O., Battari, A.E., Braguer, D., Ayeb, M.E., and Marrakchi, N. (2010). MVL-PLA2, a snake venom phospholipase A2, inhibits angiogenesis through an increase in microtubule dynamics and disorganization of focal adhesions. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010124"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"A.3M.1\u2013A.3M.13","DOI":"10.1002\/9780471729259.mca03ms22","article-title":"SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) of proteins","volume":"22","author":"Manns","year":"2011","journal-title":"Curr. Protoc. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1186\/1471-2105-14-346","article-title":"Disulfide by Design 2.0: A web-based tool for disulfide engineering in proteins","volume":"14","author":"Craig","year":"2013","journal-title":"BMC Bioinform."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"W230","DOI":"10.1093\/nar\/gki412","article-title":"DiANNA: A web server for disulfide connectivity prediction","volume":"33","author":"Clote","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/(SICI)1097-0134(19990815)36:3<340::AID-PROT8>3.0.CO;2-D","article-title":"Role of evolutionary information in predicting the disulfide-bonding state of cysteine in proteins","volume":"36","author":"Fariselli","year":"1999","journal-title":"Proteins"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/12\/859\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:38:52Z","timestamp":1760168332000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/12\/859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,2]]},"references-count":87,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["toxins13120859"],"URL":"https:\/\/doi.org\/10.3390\/toxins13120859","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,2]]}}}