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Synergism between Basic Asp49 and Lys49 Phospholipase A2 Myotoxins of Viperid Snake Venom In Vitro and In Vivo.
- Source :
- PLoS ONE; Oct2014, Vol. 9 Issue 10, p1-11, 11p
- Publication Year :
- 2014
-
Abstract
- Two subtypes of phospholipases A<subscript>2</subscript> (PLA<subscript>2</subscript>s) with the ability to induce myonecrosis, ‘Asp49’ and ‘Lys49’ myotoxins, often coexist in viperid snake venoms. Since the latter lack catalytic activity, two different mechanisms are involved in their myotoxicity. A synergism between Asp49 and Lys49 myotoxins from Bothrops asper was previously observed in vitro, enhancing Ca<superscript>2+</superscript> entry and cell death when acting together upon C2C12 myotubes. These observations are extended for the first time in vivo, by demonstrating a clear enhancement of myonecrosis by the combined action of these two toxins in mice. In addition, novel aspects of their synergism were revealed using myotubes. Proportions of Asp49 myotoxin as low as 0.1% of the Lys49 myotoxin are sufficient to enhance cytotoxicity of the latter, but not the opposite. Sublytic amounts of Asp49 myotoxin also enhanced cytotoxicity of a synthetic peptide encompassing the toxic region of Lys49 myotoxin. Asp49 myotoxin rendered myotubes more susceptible to osmotic lysis, whereas Lys49 myotoxin did not. In contrast to myotoxic Asp49 PLA<subscript>2</subscript>, an acidic non-toxic PLA<subscript>2</subscript> from the same venom did not markedly synergize with Lys49 myotoxin, revealing a functional difference between basic and acidic PLA<subscript>2</subscript> enzymes. It is suggested that Asp49 myotoxins synergize with Lys49 myotoxins by virtue of their PLA<subscript>2</subscript> activity. In addition to the membrane-destabilizing effect of this activity, Asp49 myotoxins may generate anionic patches of hydrolytic reaction products, facilitating electrostatic interactions with Lys49 myotoxins. These data provide new evidence for the evolutionary adaptive value of the two subtypes of PLA<subscript>2</subscript> myotoxins acting synergistically in viperid venoms. [ABSTRACT FROM AUTHOR]
- Subjects :
- PHOSPHOLIPASES
VIPERIDAE
SNAKE venom
PEPTIDOMIMETICS
MYOBLASTS
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 99200257
- Full Text :
- https://doi.org/10.1371/journal.pone.0109846