Monika Cecilija Žužek

Publications (2)2.51 Total impact

• Source

  Available from: Polona Juntes

  Article: Ostreolysin induces sustained contraction of porcine coronary arteries and endothelial dysfunction in middle- and large-sized vessels.

  Polona Juntes, Katja Rebolj, Kristina Sepcić, Peter Macek, Monika Cecilija Zuzek, Vojteh Cestnik, Robert Frangez
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  ABSTRACT: Ostreolysin (Oly), a cytolytic and cardiotoxic protein from the oyster mushroom (Pleurotus ostreatus), is lethal for mice with an LD(50) of 1170 microg/kg following intravenous application. Its cardiotoxicity is associated with hyperkalemia, which is probably a consequence of potassium released from the lysed cells. Moreover, sub-micromolar concentrations of Oly induce a concentration-dependent increase in rat aortic ring tension, suggesting that ischaemia, and consequent hypoxic injury of cardiomyocytes, could also derive from vasospasm induced by this toxic protein. The purpose of the present study was to demonstrate histopathological lesions caused by Oly after parenteral application to rats, and to define the mechanisms of Oly-induced vasoconstriction using inhibitors verapamil, lanthanum chloride, and selective endothelin receptor antagonist TBC3214, which have different molecular targets, in vitro on porcine coronary artery rings. We found that Oly causes endothelial injury with perivascular oedema in the heart and lungs, as well as myocardial haemorrhages in rats. Treatment of porcine coronary artery rings with Oly causes concentration-dependent vasoconstriction and prevents endothelium-mediated relaxation. Using TBC3214 as a selective blocker of the endothelin A receptor, we showed that vasoconstriction induced by Oly was independent of endothelin release and its effects. Verapamil (1 microM) greatly reduced Oly-evoked contractions of porcine coronary artery rings, while lanthanum abolished them completely. These results provide evidence that the contraction of coronary arteries by Oly is due mainly to the increased influx of Ca(2+) from the extracellular space through voltage-dependent L-type Ca(2+) channels and cation non-selective channels. Experiments suggest that Oly damages endothelial cells both in vitro and in vivo, and probably exhibits direct contractile effects on coronary smooth muscle cells.
  Toxicon 07/2009; 54(6):784-92. · 2.51 Impact Factor
• Article: Toxic and lethal effects of ostreolysin, a cytolytic protein from edible oyster mushroom (Pleurotus ostreatus), in rodents

  Monika Cecilija Žužek, Peter Maček, Kristina Sepčić, Vojteh Cestnik, Robert Frangež
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  ABSTRACT: Ostreolysin (Oly), an acidic, 15 kDa protein from the edible oyster mushroom (Pleurotus ostreatus), is a toxic, pore-forming cytolysin. In this paper, its toxic properties have been studied in rodents and the LD50 in mice shown to be 1170 μg/kg. Electrocardiogram, arterial blood pressure and respiratory activity were recorded under general anaesthesia, in intact, pharmacologically vagotomised and artificially respirated rats injected with one mouse LD50. A few seconds after intravenous Oly injection, a transient increase in arterial blood pressure was recorded, followed by a progressive fall to mid-circulatory pressure accompanied by bradicardia, myocardial ischaemia and ventricular extrasystoles. Similar changes produced by Oly were observed in vagotomised and artificially respirated animals, indicating that vagotomy and hypoxia play no primary role in toxicity. Oly induced lysis of rat erythrocytes in vitro, and probably also in vivo as indicated by the increase in serum potassium. Although direct action of the protein on the cardiomyocytes or heart circulation cannot be excluded, the hyperkalaemia resulting from the haemolytic activity probably plays an important role in its toxicity. The lethality and cardiorespiratory toxic action of Oly are thus shown to be candidates for the cause of the recorded adverse effects of oyster mushroom.
  Toxicon.