Systemic and local myotoxicity induced by snake venom group II phospholipases A2: Comparison between crotoxin, crotoxin B and a Lys49 PLA2 homologue

Gutiérrez, José Marı́a; Ponce-Soto, Luis Alberto; Marangoni, Sérgio; Lomonte, Bruno

doi:10.1016/j.toxicon.2007.08.007

Cited by 102 publications

(63 citation statements)

References 45 publications

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“…If there was a dependence on the latter, the Bj-VII K49 PLA2 homolog would not exhibit the myotoxic effect seen in Fig. 4 (Gutiérrez et al 2008). Our results show that 6-1, 6-2 (PLA2 D-49) and Bj-VII (PLA2 K-49 homolog) conform to other group II myotoxic PLA2s since they cause more local than systemic myonecrosis (Fig.…”

Section: Discussionmentioning

confidence: 55%

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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Section: Discussionmentioning

confidence: 55%

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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“…At variance, the Ca 2+ overload induced by myotoxic PLA 2 s in muscle fibers occurs throughout the length of these cells [35], causing widespread hypercontraction [104] and cell death through a variety of Ca 2+ -dependent degenerative events [25]. In the case of the Lys49 PLA 2 myotoxins, the tissue degenerates around the site of toxin injection, whilst a systemic rhabdomyolysis develops with systemic toxins such as crotoxin and various elapid PLA 2 s [25,84]. However, regardless of the local vs. systemic nature of the myotoxic effect, the mechanisms of cellular damage are similar for the two types of myotoxins.…”

Section: Membrane Damagementioning

confidence: 99%

Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action

Montecucco

Gutiérrez

Lomonte

2008

Cell. Mol. Life Sci.

261

163

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A large variety of snake toxins evolved from PLA(2) digestive enzymes through a process of 'accelerated evolution'. These toxins have different tissue targets, membrane receptors and mechanisms of alteration of the cell plasma membrane. Two of the most commonly induced effects by venom PLA(2)s are neurotoxicity and myotoxicity. Here, we will discuss how these snake toxins achieve a similar cellular lesion, which is evolutionarily highly conserved, despite the differences listed above. They cause an initial plasma membrane perturbation which promotes a large increase of the cytosolic Ca(2+) concentration leading to cell degeneration, following modes that we discuss in detail for muscle cells and for the neuromuscular junction. The different systemic pathophysiological consequences caused by these toxins are not due to different mechanisms of cell toxicity, but to the intrinsic anatomical and physiological properties of the targeted tissues and cells.

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“…The myotoxicity of CTX can be characterized as a systematic and generally irreversible damage caused to skeletal muscles. The systemic myotoxicity caused by CTX is accompanied by an increase in plasma creatinekinase and myoglobinuria, which often leads to acute renal failure [8][9][10]. Studies regarding the cardiotoxic effect of CTX showed that it induces a significant decrease in the contractile force of the heart, and causes an increase in creatine-kinase activity [11].…”

Section: Introductionmentioning

confidence: 99%

Heterologous Expression and Purification of Recombinant Crotoxin B, the Phospholipase A2 Subunit of Crotoxin

Boda¹,

Salamon²,

Orbán³

et al. 2018

Studia UBB Chemia

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ABSTRACT.Crotoxin is a heterodimeric β-neurotoxin isolated from the venom of Crotalus durissus terrificus, consisting of two, non-covalently bound subunits, crotapotin (CA) and crotoxin B (CB). Both subunits present four different isoforms, consequently there are up to 16 different crotoxin complexes, each with different activity levels. The biological activities usually associated with crotoxin include neurotoxicity, myotoxicity and cardiotoxicity, however several other important biochemical and pharmacological effects of crotoxin have been observed, such as the antibacterial, antiviral, antiinflammatory, antitumoral and analgesic activity. In this study we present the production of recombinant crotoxin B (isoform C). Expression of the protein was carried out using E. coli Rosetta TM (DE3)pLysS strain, and the obtained protein was separated and purified using Ni 2+ -affinity chromatography. To the best of our knowledge the developed method represents the first reported method for obtaining the crotoxin B (isoform C) through heterologous expression using an efficient and cost-effective procedure.

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Systemic and local myotoxicity induced by snake venom group II phospholipases A2: Comparison between crotoxin, crotoxin B and a Lys49 PLA2 homologue

Cited by 102 publications

References 45 publications

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

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

Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action

Heterologous Expression and Purification of Recombinant Crotoxin B, the Phospholipase A2 Subunit of Crotoxin

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