Rapid short term and gradual permanent cardiotoxic effects of vertebrate toxins from Chironex fleckeri (Australian box jellyfish) venom.
The vertebrate cardiotoxic components of the venom produced by the Australian box jellyfish, Chironex fleckeri, have not previously been isolated. We have uncovered for the first time, three distinct cytotoxic crude fractions from within the vertebrate cardiotoxic peak of C. fleckeri venom by monitoring viability of human muscle cells with an impedance based assay (ACEA xCELLigence system) measuring cell detachment as cytotoxicity which was correlated with a reduction in cell metabolism using a cell proliferation (MTS) assay. When the effects of the venom components on human cardiomyocytes and human skeletal muscle cells were compared, two fractions were found to specifically affect cardiomyocytes with distinct temporal profiles (labelled Crude Toxic Fractions (CTF), α and β). A third fraction (CTF-γ) was toxic to both muscle cell types and therefore not cardio specific. The vertebrate, cardio specific CTF-α and CTF-β, presented distinct activities; CTF-α caused rapid but short term cell detachment and reduction in cell metabolism with enhanced activity at lower concentrations than CTF-β. This activity was not permanent, with cell reattachment and subsequent increased metabolism of heart muscle cells observed when exposed to all but the highest concentrations of CTF-α tested. The cytotoxic effect of CTF-β took twice as long to act on the cells compared to CTF-α, however, the activity was permanent. Furthermore, we showed that the two fractions combined have a synergistic effect causing a much stronger and faster cell detachment (death) when combined than the sum of the individual effects of each toxin. These data presented here improves the current understanding of the toxic mechanisms of the Australian box jellyfish, C. fleckeri, and provides a basis for in vivo research of these newly isolated toxic fractions.
Queensland Tropical Health Alliance (QTHA), Building E4, James Cook University, McGregor Road, QLD 4878, Australia; Centre for Biodiscovery and Molecular Development of Therapeutics (CBMDT), James Cook University, McGregor Road, Cairns 4878, Australia; School of Marine and Tropical Biology, James Cook University, Smithfield, QLD, Australia. Electronic address: s.chaousis@uq.edu.au.
Stephanie
S
Chaousis
Queensland Tropical Health Alliance (QTHA), Building E4, James Cook University, McGregor Road, QLD 4878, Australia; Centre for Biodiscovery and Molecular Development of Therapeutics (CBMDT), James Cook University, McGregor Road, Cairns 4878, Australia.
Michael
M
Smout
Queensland Tropical Health Alliance (QTHA), Building E4, James Cook University, McGregor Road, QLD 4878, Australia; Centre for Biodiscovery and Molecular Development of Therapeutics (CBMDT), James Cook University, McGregor Road, Cairns 4878, Australia.
David
D
Wilson
Queensland Tropical Health Alliance (QTHA), Building E4, James Cook University, McGregor Road, QLD 4878, Australia; Centre for Biodiscovery and Molecular Development of Therapeutics (CBMDT), James Cook University, McGregor Road, Cairns 4878, Australia.
Alex
A
Loukas
Centre for Biodiscovery and Molecular Development of Therapeutics (CBMDT), James Cook University, McGregor Road, Cairns 4878, Australia.
Jason
J
Mulvenna
Queensland Tropical Health Alliance (QTHA), Building E4, James Cook University, McGregor Road, QLD 4878, Australia; Centre for Biodiscovery and Molecular Development of Therapeutics (CBMDT), James Cook University, McGregor Road, Cairns 4878, Australia; School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, McGregor Road, Cairns 4878, Australia.
Jamie
J
Seymour
D000818:Animals; D001315:Australia; D054715:Cardiotoxins / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003064:Cnidarian Venoms / Q000633:toxicity*; D037462:Cubozoa / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology
D054715:Cardiotoxins; D003064:Cnidarian Venoms
Cardiotoxic; Chironex fleckeri; Human cardiomyocytes; Human skeletal muscle cells; Venom; xCELLigence