Comparative study of the cytolytic activity of myotoxic phospholipases A2 on mouse endothelial (tEnd) and skeletal muscle (C2C12) cells in vitro

Lomonte, Bruno; Angulo, Yamileth; Rufini, Stefano; Cho, Wonhwa; Giglio, José Roberto; Ohno, Motonori; Daniele, José J.; Geoghegan, Patricia; Gutiérrez, José Marı́a

doi:10.1016/s0041-0101(98)00171-8

Cited by 147 publications

(99 citation statements)

References 48 publications

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“…platura coincides with that of notexin, a potent myotoxic PLA 2 from the Australian terrestrial elapid Notechis scutatus [63,64] which was reported to lack cytotoxicity upon myogenic and other cell lines using the same method here tested [40,65]. This finding is in sharp contrast with PLA 2 myotoxins from viperid venoms, which induce a rapid cytolytic effect upon myogenic cells and other cell types [40,65].…”

Section: Accepted M Manuscriptsupporting

confidence: 65%

“…This finding is in sharp contrast with PLA 2 myotoxins from viperid venoms, which induce a rapid cytolytic effect upon myogenic cells and other cell types [40,65]. Such functional difference suggests that myotoxicity of some elapid (group I) and viperid (group II) PLA 2 s, despite leading to a similar pathological outcome, may involve distinct molecular mechanisms, in line with the convergent evolutionary processes that independently led to the acquisition of this toxic effect in these two groups of PLA 2 s [66].…”

Section: Accepted M Manuscriptcontrasting

confidence: 63%

“…Differentiation of cultured myoblasts into myotubes has been shown to increase their susceptibility to certain myotoxins of snake venoms [40,62]. Exposure of differentiated myotubes to P. platura venom also led to negative results (data not shown),…”

Section: Accepted M Manuscriptmentioning

confidence: 86%

“…The cytotoxic effect of the venom was assayed on the murine myogenic cell line C2C12 (ATCC CRL-1772), as described [40]. Varying amounts of venom, diluted in 150…”

Section: Cytotoxic Activitymentioning

confidence: 99%

See 3 more Smart Citations

Two color morphs of the pelagic yellow-bellied sea snake, Pelamis platura, from different locations of Costa Rica: Snake venomics, toxicity, and neutralization by antivenom

Lomonte

Plá

Sasa

et al. 2014

Journal of Proteomics

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Section: Accepted M Manuscriptsupporting

confidence: 65%

Section: Accepted M Manuscriptcontrasting

confidence: 63%

Section: Accepted M Manuscriptmentioning

confidence: 86%

“…The cytotoxic effect of the venom was assayed on the murine myogenic cell line C2C12 (ATCC CRL-1772), as described [40]. Varying amounts of venom, diluted in 150…”

Section: Cytotoxic Activitymentioning

confidence: 99%

See 2 more Smart Citations

Two color morphs of the pelagic yellow-bellied sea snake, Pelamis platura, from different locations of Costa Rica: Snake venomics, toxicity, and neutralization by antivenom

Lomonte

Plá

Sasa

et al. 2014

Journal of Proteomics

Self Cite

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“…These distinct effects might be due to the specificity of these myotoxins for differentiated muscle cells, i.e. on their affinity for highly specific targets in muscle cell plasma membrane (Gutierrez and Ownby, 2003) and also for targeting other cell types (Lomonte et al, 1994(Lomonte et al, , 1999.…”

Section: Discussionmentioning

confidence: 99%

Effect of calcineurin inhibitors on myotoxic activity of crotoxin and Bothrops asper phospholipase A2 myotoxins in vivo and in vitro

Miyabara¹,

Baptista²,

Lomonte³

et al. 2006

Comparative Biochemistry and Physiology Part C: Toxicology &

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Previous studies have shown that calcineurin activity plays a critical role in the myotoxic activity induced by crotoxin (CTX), a group II phospholipase A 2 (PLA 2 ) with neurotoxic and myotoxic actions. In order to address whether calcineurin is also important for the activity of nonneurotoxic group II PLA 2 myotoxins we have compared the effects of calcineurin inhibition on the myotoxic capacity of CTX and the nonneurotoxic PLA 2 s, myotoxin II (Mt II) and myotoxin III (Mt III) from Bothrops asper venom. Rats were treated with cyclosporin A (CsA) or FK506, calcineurin inhibitors, and received an intramuscular injection of either CTX, Mt II or Mt III into the tibialis anterior. Animals were killed 24 h after injection of toxins. Tibialis anterior was removed and stored in liquid nitrogen. Myofibers in culture were also treated with CsA or FK506 and exposed to CTX, Mt II and Mt III. It was observed that, in contrast to CTX, CsA and FK506 do not attenuate myotoxic effects induced by both Mt II and Mt III in vivo and in vitro. The results of the present study suggest that calcineurin is not essential for the myotoxic activity of Mt II and Mt III, indicating that distinct intracellular pathways might be involved in myonecrosis induced by neurotoxic CTX and non-neurotoxic Bothrops sp. PLA 2 myotoxins. Alternatively, calcineurin dependent fast fiber type shift might render the muscle resistant to the action of CTX, without affecting its susceptibility to Bothrops sp. myotoxins.

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Membrane-perturbing activity ofViperidae myotoxins: an electrostatic surface potential approach to a puzzling problem

2000

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Phospholipase-like myotoxins are a class of proteins present in Viperidae venom. Despite the high level of amino acid and structural homology with soluble phospholipases A(2), myotoxins are devoid of enzymatic activity and share cytolytic activity by means of a totally unknown mechanism involving the lipid bilayer perturbation. The distribution of electrostatic surface potentials of four myotoxins and seven phospholipases A(2) has been compared. The charge distribution is similar in all active non-cytolytic phospholipases with a strongly positive side corresponding to the domain interacting with the micellar substrate and with the opposite side negatively charged. In contrast, all myotoxins examined are positively charged on both sides. Myotoxin III, the only known example of a myotoxin sharing enzymatic activity, displays the same electrostatic surface potential as other related toxins. Using liposomes made with non-hydrolysable phospholipids, we demonstrate that myotoxin III perturbs the lipid bilayer like other myotoxins. Based on these results, a molecular model for myotoxin-membrane perturbing activity is proposed. In this model, potential double-face binding of myotoxic phospholipases A(2) to lipid surfaces could trigger a lipid bilayer destabilization and could generate a stable fusion pore, probably because of the presence of hydrophobic moieties that flank the cationic sites.

show abstract

Comparative study of the cytolytic activity of myotoxic phospholipases A2 on mouse endothelial (tEnd) and skeletal muscle (C2C12) cells in vitro

Cited by 147 publications

References 48 publications

Two color morphs of the pelagic yellow-bellied sea snake, Pelamis platura, from different locations of Costa Rica: Snake venomics, toxicity, and neutralization by antivenom

Two color morphs of the pelagic yellow-bellied sea snake, Pelamis platura, from different locations of Costa Rica: Snake venomics, toxicity, and neutralization by antivenom

Effect of calcineurin inhibitors on myotoxic activity of crotoxin and Bothrops asper phospholipase A2 myotoxins in vivo and in vitro

Membrane-perturbing activity ofViperidae myotoxins: an electrostatic surface potential approach to a puzzling problem

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