Crude venom from nematocysts of Pelagia noctiluca (Cnidaria: Scyphozoa) elicits a sodium conductance in the plasma membrane of mammalian cells

Rossana Morabito,Silvia Dossena,Charity Nofziger,Valentina Rizzo,Roberta Costa,Alessia Remigante,Markus Paulmichl,Angela Marino,Giuseppa La Spada

doi:10.1038/srep41065

Rossana Morabito, Silvia Dossena + Show 7 more

Open Access

https://doi.org/10.1038/srep41065

Copy DOI

Abstract

Cnidarians may negatively impact human activities and public health but concomitantly their venom represents a rich source of bioactive substances. Pelagia noctiluca is the most venomous and abundant jellyfish of the Mediterranean Sea and possesses a venom with hemolytic and cytolytic activity for which the mechanism is largely unknown. Here we show that exposure of mammalian cells to crude venom from the nematocysts of P. noctiluca profoundly alters the ion conductance of the plasma membrane, therefore affecting homeostatic functions such as the regulation and maintenance of cellular volume. Venom-treated cells exhibited a large, inwardly rectifying current mainly due to permeation of Na+ and Cl−, sensitive to amiloride and completely abrogated following harsh thermal treatment of crude venom extract. Curiously, the plasma membrane conductance of Ca2+ and K+ was not affected. Current-inducing activity was also observed following delivery of venom to the cytosolic side of the plasma membrane, consistent with a pore-forming mechanism. Venom-induced NaCl influx followed by water and consequent cell swelling most likely underlie the hemolytic and cytolytic activity of P. noctiluca venom. The present study underscores unique properties of P. noctiluca venom and provides essential information for a possible use of its active compounds and treatment of envenomation.

Highlights

Cnidarians may negatively impact human activities and public health but concomitantly their venom represents a rich source of bioactive substances
Consequences of Cnidaria stings may range from minor local irritation to severe local and systemic reactions including excruciating pain and life-threatening cardiovascular collapse depending on the Cnidarian species, age of the victim and size of the area contacted
Abnormal proliferation of this jellyfish in the Mediterranean basin represented a remarkable threat to the public health and caused substantial economical burden by interfering with human activities such as tourism and fishery, arousing increasing interest on the toxicological properties of its venom[12]

Summary

Introduction

Cnidarians may negatively impact human activities and public health but concomitantly their venom represents a rich source of bioactive substances. Cnidarians venom is a rich source of bioactive substances that may have therapeutic potential and other useful applications[5,6,7] Owing to their activity on voltage-gated ion channels in the central nervous system and transmitter release at the neuromuscular junction, Cnidaria toxins can substantially contribute to the development of lead compounds for the treatment of pain and some neurological and neurodegenerative diseases[6,7]. Abnormal proliferation of this jellyfish in the Mediterranean basin represented a remarkable threat to the public health and caused substantial economical burden by interfering with human activities such as tourism and fishery, arousing increasing interest on the toxicological properties of its venom[12]. Intravenous injection of crude venom in rats evoked a systemic inflammatory response along with increased plasma levels of nitric oxide and ROS as well as cellular infiltration, increased cyclooxygenase expression, lipid peroxidation and induction of apoptosis in the lung and intestine[26]

Methods

Results

Conclusion