Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants

Chacur, Marucia; Longo, I.; Picolo, Gisele; Gutiérrez, José Marı́a; Lomonte, Bruno; Guerra, José Luiz; Teixeira, Catarina; Cury, Yara

doi:10.1016/s0041-0101(03)00007-2

Cited by 94 publications

(84 citation statements)

References 52 publications

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“…Previous studies have implicated several mediators in the onset of pain induced by these myotoxins (8,44,45). The present findings of K + and ATP release provide a novel basis for the strong pain sensation reported by bitten individuals.…”

Section: +supporting

confidence: 57%

Bothrops snake myotoxins induce a large efflux of ATP and potassium with spreading of cell damage and pain

Cintra-Francischinelli

Caccin²,

Chiavegato³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Myotoxins play a major role in the pathogenesis of the envenomations caused by snake bites in large parts of the world where this is a very relevant public health problem. We show here that two myotoxins that are major constituents of the venom of Bothrops asper, a deadly snake present in Latin America, induce the release of large amounts of K + and ATP from skeletal muscle. We also show that the released ATP amplifies the effect of the myotoxins, acting as a "danger signal," which spreads and causes further damage by acting on purinergic receptors. In addition, the release of ATP and K + well accounts for the pain reaction characteristic of these envenomations. As Bothrops asper myotoxins are representative of a large family of snake myotoxins with phospholipase A 2 structure, these findings are expected to be of general significance for snake bite envenomation. Moreover, they suggest potential therapeutic approaches for limiting the extent of muscle tissue damage based on antipurinergic drugs. muscle damage | phospholipase A2 | C2C12 cells

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Section: +supporting

confidence: 57%

Bothrops snake myotoxins induce a large efflux of ATP and potassium with spreading of cell damage and pain

Cintra-Francischinelli

Caccin²,

Chiavegato³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…According to the literature, edema is one of the characteristic effects of an inflammatory scenario, and the edema caused by poisons is due, in part, to the ability of venom to stimulate the release of eicosanoids (Chaves et al 1995). The ability of Asp49 and Lys49 basic PLA2 from snake venoms to induce membrane disruption in skeletal muscle cells in vivo and in vitro (Gutierrez and Ownby 2003) as well as to induce inflammatory reactions associated with edema, cellular infiltration (Castro et al 2000) and pain (Chacur et al 2003) has been widely demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Toxicity of phospholipases A2 D49 (6-1 and 6-2) and K49 (Bj-VII) from Bothrops jararacussu venom

et al. 2008

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Purified phospholipase A2 (PLA2) enzymes from Bothrops jararacussu snake venom were examined to evaluate NIH 3T3 and COS7 fibroblast cytotoxicity, as well as muscle myotoxic and inflammatory activities. Separation of fractions Bj-VII (from BthTX-I; a Lys49 PLA2 homolog) and 6-1 and 6-2 (from BthTX-II; an Asp49 PLA2) from B. jararacussu snake venom by SDS-PAGE in tricine buffer in the absence and presence of dithiothreitol revealed a homodimer with an estimated molecular mass of approximately 30 kDa (monomer mass approximately 15 kDa). This finding indicates that these toxins form dimeric complexes-a previously reported tendency among PLA2s. These toxins were assayed for viability with the MTT assay, which is used to examine the effects of phospholipases on the mitochondrial viability of cells. The toxins were also assayed for cytolysis of the fibroblast cell lines NIH 3T3 and COS7 by quantification of lactate dehydrogenase released into the medium. The results indicate that the PLA2s 6-1, 6-2 and the Bj-VII PLA2 homolog studied here induce moderate footpad edema and local myotoxicity. Moreover, exposure to these phospholipases led to a reduction in fibroblast viability; at the 1 muM dose of PLA2 tested, a reduction of 50% in cell viability was observed. The present findings indicate that the inflammatory activity observed in envenomation may be correlated with the cytotoxicity observed in fibroblasts.

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“…These events are accompanied by an acute inflammatory reaction associated with swelling, pain and the recruitment of macrophages and polymorphonuclear leukocytes (Chacur et al, 2003;Gutierrez et al, 2009;Mamede et al, 2013). Activated leukocytes secrete a wide range of chemical mediators such as IL-1, IL-6 and IL-8, which along with the biological effects induced by the toxin, may contribute to the evolution of local myotoxicity and regeneration Voronov et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Biochemical and functional studies of ColTx-I, a new myotoxic phospholipase A2 isolated from Crotalus oreganus lutosus (Great Basin rattlesnake) snake venom

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Silva

et al. 2016

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Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants

Cited by 94 publications

References 52 publications

Bothrops snake myotoxins induce a large efflux of ATP and potassium with spreading of cell damage and pain

Bothrops snake myotoxins induce a large efflux of ATP and potassium with spreading of cell damage and pain

Toxicity of phospholipases A2 D49 (6-1 and 6-2) and K49 (Bj-VII) from Bothrops jararacussu venom

Biochemical and functional studies of ColTx-I, a new myotoxic phospholipase A2 isolated from Crotalus oreganus lutosus (Great Basin rattlesnake) snake venom

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