Stonustoxin

Stonustoxin (SNTX) is an extremely potent cytolytic toxin of the perforin-like superfamily. It is mainly found in stonefish (Synanceia). The name Stonustoxin is an abbreviation of STOnefish National University of Singapore.

History

Little is known about the biological activity and composition of marine fish venoms, due to the difficulties in obtaining, storing and extracting venom samples. The National University of Singapore performed the first purification of the stonefish venom, because stonefish stings have been responsible for a number of deaths and severe poisoning cases in the local area. The molecular weight was determined by high performance liquid chromatography at pH 7.0 using 10 mM sodium phosphate buffer with 0.2M sodium sulfate in a gel permeation column at a flow rate of 1.0 ml/min.

Structure

The exact conformation of stonustoxin has been described.[1] Stonustoxin is a heterodimer composed of stonustoxin-a and stonustoxin-ß. The tertiary structure of each subunit possesses a domain capable of binding to cellular membranes, and a domain securing the structure of the protein itself. The quaternary structure of stonustoxin can be described as a large pore. The subunits forming said pore are held together by weak intermolecular forces such as hydrogen bonds.

Mechanism of action

Stonustoxin contains an N-terminal domain homologous to the MACPF. When this domain comes into contact with tissues of a victim, the MACPF domain enables stonustoxin to adhere to a cellular membrane and form a pore, generally leading to cellular death. This particular pore forming ability can be used on a large variety of tissues, explaining the many different physiological responses.[1] The formation of pores in capillaries, for example, is the cause of hypotension caused by stonefish envenomation.

Adverse effects

The venom of the stonefish consists of different toxins, which enhance each other's destructive ability. Besides stonustoxin, it also contains hyaluronidase and cardioleputin. Hyaluronidase damages the tissue surrounding the sting, causing a burning, stinging sensation. Stonustoxine increases the blood vessel's permeability and dilates capillaries, enabling a faster distribution of the venom. Finally, cardioleputin increases heart rate which further speeds up the distribution of the venom throughout the entire bloodstream. The dilation of capillaries is the cause of the hypotension. At first, it was thought that the impairment of the respiratory system due to paralysis of the skeletal muscles was the main cause of death in stonefish venom envenomation cases, however, it was found that hypotension was the main cause of the venom's lethality (Low, 1993). Envenomation by the stonefish will result in extreme pain, edema, hypotension, respiratory distress, internal bleeding, and in some occasions, death.

Treatment and metabolism

There is an antivenom for stonefish envenomation, but since it has to be kept away from light at temperatures between 0 °C and 5 °C, delivery of the antivenom to the tropical regions where stonefish stings occur is often very problematic. However, immersion in hot water has been tested as a way of rendering stonustoxin inactive. Since stonustoxin is composed of various subunits, it is susceptible to structural changes caused by heat. The weak intermolecular forces connecting the tertiary and quaternary structures are weakened by extreme heat. If the temperature limits are exceeded, stonustoxin could lose its function. An attempt at protein denaturation to treat stonefish stings made by Darlene and Phee-Keng.[2] When a 47-year-old woman stung by a stonefish while diving was brought to the hospital, various anesthetics were administered but her pain remained severe. Her foot was later immersed in a tub of hot water. Temperatures were kept as high as possible without scalding the patient. After an hour of immersion, her pain was substantially relieved and swelling decreased.

References

1. Johnson DA, Sreebny LM (February 1973). "Effect of isoproterenol on synthesis and secretion in the rat parotid gland". Laboratory Investigation; A Journal of Technical Methods and Pathology. 28 (2): 263–9. PMID 4687532.
2. Darlene FO, Phee-Kheng C (30 April 2013). "Hot water immersion as a treatment for stonefish sting: A case report". Malaysian Family Physician. 8 (1): 28–32. PMC 4170453. PMID 25606265.

Further reading

• Ellisdon AM, Reboul CF, Panjikar S, Huynh K, Oellig CA, Winter KL, Dunstone MA, Hodgson WC, Seymour J, Dearden PK, Tweten RK, Whisstock JC, McGowan S (December 2015). "Stonefish toxin defines an ancient branch of the perforin-like superfamily". Proceedings of the National Academy of Sciences of the United States of America. 112 (50): 15360–5. doi:10.1073/pnas.1507622112. PMC 4687532. PMID 26627714.
• Church JE, Hodgson WC (August 2002). "The pharmacological activity of fish venoms". Toxicon. 40 (8): 1083–93. doi:10.1016/S0041-0101(02)00126-5. PMID 12165309.
• Low KS, Gwee MC, Yuen R, Gopalakrishnakone P, Khoo HE (November 1993). "Stonustoxin: a highly potent endothelium-dependent vasorelaxant in the rat". Toxicon. 31 (11): 1471–8. doi:10.1016/0041-0101(93)90212-2. PMID 8310447.
• Poh CH, Yuen R, Khoo HE, Chung M, Gwee M, Gopalakrishnakone P (1991). "Purification and partial characterization of stonustoxin (lethal factor) from Synanceja horrida venom". Comparative Biochemistry and Physiology. B, Comparative Biochemistry. 99 (4): 793–8. doi:10.1016/0305-0491(91)90143-2. PMID 1790672.