Cardiovascular effects of Sp-CTx, a cytolysin from the scorpionfish (Scorpaena plumieri) venom

Toxicon. 2016 Aug:118:141-8. doi: 10.1016/j.toxicon.2016.05.002. Epub 2016 May 4.

Abstract

Fish venom cytolysins are multifunctional proteins that in addition to their cytolytic/hemolytic effects display neurotoxic, cardiotoxic and inflammatory activities, being described as "protein lethal factors". A pore-forming cytolysin called Sp-CTx (Scorpaena plumieriCytolytic Toxin) has been recently purified from the venom of the scorpionfish Scorpaena plumieri. It is a glycoprotein with dimeric constitution, comprising subunits of approximately 65 kDa. Previous studies have revealed that this toxin has a vasorelaxant activity that appears to involve the L-arginine-nitric oxide synthase pathway; however its cardiovascular effects have not been fully comprehended. The present study examined the cardiovascular effects of Sp-CTx in vivo and in vitro. In anesthetized rats Sp-CTx (70 μg/kg i.v) produced a biphasic response which consisted of an initial systolic and diastolic pressure increase followed by a sustained decrease of these parameters and the heart rate. In isolated rats hearts Sp-CTx (10(-9) to 5 × 10(-6) M) produced concentration-dependent and transient ventricular positive inotropic effect and vasoconstriction response on coronary bed. In papillary muscle, Sp-CTx (10(-7) M) also produced an increase in contractile isometric force, which was attenuated by the catecholamine releasing agent tyramine (100 μM) and the β-adrenergic antagonist propranolol (10 μM). On isolated ventricular cardiomyocytes Sp-CTx (1 nM) increased the L-type Ca(2+) current density. The results show that Sp-CTx induces disorders in the cardiovascular system through increase of sarcolemmal calcium influx, which in turn is partially caused by the release of endogenous noradrenaline.

Keywords: Cardiotoxic; Cytolysin; Fish venom; Scorpaena plumieri.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Brazil
  • Cardiotoxins / administration & dosage
  • Cardiotoxins / isolation & purification
  • Cardiotoxins / toxicity*
  • Cells, Cultured
  • Coronary Circulation / drug effects*
  • Fish Proteins / administration & dosage
  • Fish Proteins / isolation & purification
  • Fish Proteins / toxicity
  • Fish Venoms / chemistry*
  • Glycoproteins / administration & dosage
  • Glycoproteins / isolation & purification
  • Glycoproteins / toxicity
  • Heart / drug effects*
  • Heart / physiology
  • Heart Rate / drug effects
  • In Vitro Techniques
  • Injections, Intravenous
  • Male
  • Muscle Contraction / drug effects
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Papillary Muscles / drug effects*
  • Papillary Muscles / physiology
  • Patch-Clamp Techniques
  • Perciformes*
  • Perforin / administration & dosage
  • Perforin / isolation & purification
  • Perforin / toxicity*
  • Rats, Wistar
  • Vasoconstrictor Agents / administration & dosage
  • Vasoconstrictor Agents / isolation & purification
  • Vasoconstrictor Agents / toxicity

Substances

  • Cardiotoxins
  • Fish Proteins
  • Fish Venoms
  • Glycoproteins
  • Vasoconstrictor Agents
  • Perforin