Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins.

Robert Frangež (1) , Dušan Šuput (2, 1) , Jordi Molgó (3) , Evelyne Benoit (4, 3)

1 University of Ljubljana
2 Institute for Pathophysiology
3 NeuroPSI - Institut des Neurosciences Paris-Saclay
4 SIMoS - Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO)

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Mots clés: biological effects; equinatoxins; ostreolysin A/pleurotolysin B; pore-forming proteins

Domaines: Neurobiologie; Psychologie et comportements; Sciences cognitives

Robert Frangež, Dušan Šuput, Jordi Molgó, Evelyne Benoit. Ostreolysin A/Pleurotolysin B and Equinatoxins: Structure, Function and Pathophysiological Effects of These Pore-Forming Proteins.. Toxins, 2017, 9 (4), ⟨10.3390/toxins9040128⟩. ⟨hal-01572247⟩