Cardiotoxin III (CTX III, also known as cytotoxin 3) is a sixty amino-acid

polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

from the Taiwan cobra '' Naja atra''. CTX III is highly basic and hydrophobic protein. It is an example of a group of snake cardio/ cytotoxins ( InterPro: ''IPR003572''), which are made up of shorter

snake venom Snake venom is a highly toxic saliva containing zootoxins that facilitates in the immobilization and digestion of prey. This also provides defense against threats. Snake venom is usually injected by unique fangs during a Snakebite, bite, though ...

three-finger toxins. Over 50 different cytotoxin polypeptides have been isolated and sequenced from venom samples. The difference in the CTX functionality may be due to the relatively small difference in the polypeptide's structure, allowing different CTXs to induce lysis in different cell types. The CTX III molecule contains multiple binding sites and is cytolytic for myocardial cells and human leukemic T cells. CTX III's molecular structure displays a folding of the polypeptide backbone that creates five stands from a globular structure. These strands form a double and a triple antiparallel β-sheet. Studies performed with an antibody complementary of CTX III seemed to conclude that the active site for the molecule's hemolytic and cytotoxic functions and characteristics result from two separate sites.

Biological research

Recent evidence has shown that CTX III may induce

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

in K562 cells via the release of cytochrome c. Results indicate that the mechanism utilized by CTX III was a ROS-independent mitochondrial dysfunction pathway. Evidence from a Taiwanese study of CTX III suggest that the polypeptide selectively enhances

induction in CD8⁺ T cells. Another study performed using

MDA-MB-231 Scientists study the behaviour of isolated cells grown in the laboratory for insights into how cells function in the body in health and disease. Experiments using cell culture are used for developing new diagnostic tests and new treatments for dise ...

breast cancer cells concluded that CTX III could induce apoptosis via concomitant inactivation of the JAK2,

STAT3 Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which in humans is encoded by the ''STAT3'' gene. It is a member of the STAT protein family. Function STAT3 is a member of the STAT protein family. In respon ...

PI3K Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...

, and Akt signaling pathways. In Colo205, human colorectal cancer cells, CTX III was found to induce apoptosis. HepG2, a type of carcinoma cell found in humans, was found to undergo apoptosis through S phase arrest when exposed to isolated toxin samples. The toxin's membrane disturbing activity was found not necessary in inducing cell death in a study using U937 cells via the Ca2+/PP2A/AMPK axis.

References

Snake toxins Peripheral membrane proteins {{membrane-protein-stub