Alternagin-C (ALT-C), a disintegrin-like protein from Rhinocerophis alternatus snake venom promotes positive inotropism and chronotropism in fish heart

Toxicon. 2016 Feb:110:1-11. doi: 10.1016/j.toxicon.2015.11.012. Epub 2015 Nov 22.

Abstract

Alternagin-C (ALT-C) is a disintegrin-like protein purified from the venom of the snake, Rhinocerophis alternatus. Recent studies showed that ALT-C is able to induce vascular endothelial growth factor (VEGF) expression, endothelial cell proliferation and migration, angiogenesis and to increase myoblast viability. This peptide, therefore, can play a crucial role in tissue regeneration mechanisms. The aim of this study was to evaluate the effects of a single dose of alternagin-C (0.5 mg kg(-1), via intra-arterial) on in vitro cardiac function of the freshwater fish traíra, Hoplias malabaricus, after 7 days. ALT-C treatment increased the cardiac performance promoting: 1) significant increases in the contraction force and in the rates of contraction and relaxation with concomitant decreases in the values of time to the peak tension and time to half- and 90% relaxation; 2) improvement in the cardiac pumping capacity and maximal electrical stimulation frequency, shifting the optimum frequency curve upward and to the right; 3) increases in myocardial VEGF levels and expression of key Ca(2+)-cycling proteins such as SERCA (sarcoplasmic reticulum Ca(2+)-ATPase), PLB (phospholamban), and NCX (Na(+)/Ca(2+) exchanger); 4) abolishment of the typical negative force-frequency relationship of fish myocardium. In conclusion, this study indicates that ALT-C improves cardiac function, by increasing Ca(2+) handling efficiency leading to a positive inotropism and chronotropism. The results suggest that ALT-C may lead to better cardiac output regulation indicating its potential application in therapies for cardiac contractile dysfunction.

Keywords: ALT-C; Heart function; Myocardial contractility; NCX; SERCA; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaculture
  • Bothrops*
  • Calcium-Binding Proteins / agonists
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / isolation & purification
  • Cardiotonic Agents / pharmacology*
  • Characiformes
  • Crotalid Venoms / chemistry
  • Disintegrins / administration & dosage
  • Disintegrins / isolation & purification
  • Disintegrins / pharmacology*
  • Fish Proteins / agonists
  • Fish Proteins / genetics
  • Fish Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Heart Rate / drug effects*
  • Heart Ventricles / drug effects*
  • Heart Ventricles / enzymology
  • Heart Ventricles / metabolism
  • Injections, Intra-Arterial
  • Myocardial Contraction / drug effects*
  • Random Allocation
  • Reptilian Proteins / administration & dosage
  • Reptilian Proteins / isolation & purification
  • Reptilian Proteins / pharmacology*
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / chemistry
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Sodium-Calcium Exchanger / agonists
  • Sodium-Calcium Exchanger / genetics
  • Sodium-Calcium Exchanger / metabolism
  • Vascular Endothelial Growth Factor A / agonists
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Ventricular Function / drug effects

Substances

  • Calcium-Binding Proteins
  • Cardiotonic Agents
  • Crotalid Venoms
  • Disintegrins
  • Fish Proteins
  • Reptilian Proteins
  • Sodium-Calcium Exchanger
  • Vascular Endothelial Growth Factor A
  • alternagin-C
  • phospholamban
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases