Cardiotoxin III

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Cytotoxin 3
Cardiotoxina III.gif
Identifiers
Organism Naja atra
Symbol?
PDB 1H0J
UniProt P60301
Search for
Structures Swiss-model
Domains InterPro

Cardiotoxin III (CTX III, also known as cytotoxin 3) is a sixty amino-acid polypeptide toxin from the Taiwan cobra Naja atra . CTX III is highly basic and hydrophobic protein. [1] It is an example of a group of snake cardio/cytotoxins (InterPro: IPR003572), which are made up of shorter snake venom 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. [2] The CTX III molecule contains multiple binding sites and is cytolytic for myocardial cells and human leukemic T cells. [3]

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. [4] 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

Cardiotoxin III pathway to induce apoptosis in U937, human leukemia cells. CTX III Pathway in U937.png
Cardiotoxin III pathway to induce apoptosis in U937, human leukemia cells.

Recent evidence has shown that CTX III may induce apoptosis 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 apoptosis induction in CD8+ T cells. [5] Another study performed using MDA-MB-231 breast cancer cells concluded that CTX III could induce apoptosis via concomitant inactivation of the JAK2, STAT3, PI3K, and Akt signaling pathways. [6] 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. [7] 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. [8]

Related Research Articles

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Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved venom apparatus, such as fangs or a stinger, in a process called envenomation. Venom is often distinguished from poison, which is a toxin that is passively delivered by being ingested, inhaled, or absorbed through the skin, and toxungen, which is actively transferred to the external surface of another animal via a physical delivery mechanism.

<span class="mw-page-title-main">Cytotoxic T cell</span> T cell that kills infected, damaged or cancerous cells

A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.

<span class="mw-page-title-main">Snake venom</span> Highly modified saliva containing zootoxins

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 injected by unique fangs during a bite, whereas some species are also able to spit venom.

<span class="mw-page-title-main">Bufotalin</span> Chemical compound

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<span class="mw-page-title-main">Chinese red-headed centipede</span> Subspecies of centipede

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<span class="mw-page-title-main">Indian cobra</span> Species of snake

The Indian cobra, also known commonly as the spectacled cobra, Asian cobra, or binocellate cobra, is a species of cobra, a venomous snake in the family Elapidae. The species is native to the Indian subcontinent, and is a member of the "big four" species that are responsible for the most snakebite cases in India.

<span class="mw-page-title-main">Caspian cobra</span> Species of snake

The Caspian cobra, also called the Central Asian cobra, ladle snake, Oxus cobra, or Russian cobra, is a species of highly venomous snake in the family Elapidae. The species is endemic to Central Asia. Described by Karl Eichwald in 1831, it was for many years considered a subspecies of the Indian cobra until genetic analysis revealed it to be a distinct species.

Taicatoxin (TCX) is a snake toxin that blocks voltage-dependent L-type calcium channels and small conductance Ca2+-activated K+ channels. The name taicatoxin (TAIpan + CAlcium + TOXIN) is derived from its natural source, the taipan snake, the site of its action, calcium channels, and from its function as a toxin. Taicatoxin was isolated from the venom of Australian taipan snake, Oxyuranus scutellatus scutellatus. TCX is a secreted protein, produced in the venom gland of the snake.

Tityustoxin is a toxin found in the venom of scorpions from the subfamily Tityinae. By binding to voltage-dependent sodium ion channels and potassium channels, they cause sialorrhea, lacrimation and rhinorrhea.

<span class="mw-page-title-main">Chinese cobra</span> Species of snake

The Chinese cobra, also called the Taiwan cobra, is a species of cobra in the family Elapidae, found mostly in southern China and a couple of neighboring nations and islands. It is one of the most prevalent venomous snakes in China and Taiwan, which has caused many snakebite incidents to humans.

<span class="mw-page-title-main">Snake H/ACA box small nucleolar RNA</span>

In molecular biology, Snake H/ACA box small nucleolar RNA refers to a number of very closely related non-coding RNA (ncRNA) genes identified in snakes which have been predicted to be small nucleolar RNAs (snoRNAs). This type of ncRNA is involved in the biogenesis of other small nuclear RNAs and are often referred to as 'guide' RNAs. They are usually located in the nucleolus of the eukaryotic cell which is a major site of snRNA biogenesis.

<span class="mw-page-title-main">Nuclear receptor 4A1</span> Mammalian protein found in Homo sapiens

The nuclear receptor 4A1 also known as Nur77, TR3, and NGFI-B is a protein that in humans is encoded by the NR4A1 gene.

<span class="mw-page-title-main">Cobratoxin</span> Chemical compound

α-Cobratoxin is a substance of the venom of certain Naja cobras. It is a nicotinic acetylcholine receptor (nAChR) antagonist which causes paralysis by preventing the binding of acetylcholine to the nAChR.

β-Bungarotoxin Chemical compound

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Bestoxin is a neurotoxin from the venom of the South African spitting scorpion Parabuthus transvaalicus. Most likely, it targets sodium channel function, thus promoting spontaneous and repetitive neuronal firing. Following injection into mice, it causes non-lethal writhing behaviour.

Raventoxins are neurotoxins from the venom of the spider Macrothele raveni.

<span class="mw-page-title-main">Three-finger toxin</span> Toxin protein

Three-finger toxins are a protein superfamily of small toxin proteins found in the venom of snakes. Three-finger toxins are in turn members of a larger superfamily of three-finger protein domains which includes non-toxic proteins that share a similar protein fold. The group is named for its common structure consisting of three beta strand loops connected to a central core containing four conserved disulfide bonds. The 3FP protein domain has no enzymatic activity and is typically between 60-74 amino acid residues long. Despite their conserved structure, three-finger toxin proteins have a wide range of pharmacological effects. Most members of the family are neurotoxins that act on cholinergic intercellular signaling; the alpha-neurotoxin family interacts with muscle nicotinic acetylcholine receptors (nAChRs), the kappa-bungarotoxin family with neuronal nAChRs, and muscarinic toxins with muscarinic acetylcholine receptors (mAChRs).

Mipartoxin-I is a neurotoxin produced by Micrurus mipartitus, a venomous coral snake distributed in Central and South America. This toxin causes a neuromuscular blockade by blocking the nicotinic acetylcholine receptor. It is the most abundant component in the venom.

<span class="mw-page-title-main">Javan spitting cobra</span> Species of snake

The Javan spitting cobra, also called Indonesian cobra or Komodo spitting cobra, is a species of cobra in the family Elapidae, found in the Lesser Sunda Islands of Indonesia, including Java, Bali, Lombok, Sumbawa, Flores, Komodo, and others.

References

  1. Su, Shu-Hui; Su, Shu-Jem; Lin, Shinne-Ren; Chang, Kee-Lung (November 2003). "Cardiotoxin-III selectively enhances activation-induced apoptosis of human CD8+ T lymphocytes". Toxicology and Applied Pharmacology. 193 (1): 97–105. doi:10.1016/S0041-008X(03)00327-2. PMID   14613720.
  2. Ménez, A.; Gatineau, E.; Roumestand, C.; Harvey, A.L.; Mouawad, L.; Gilquin, B.; Toma, F. (August 1990). "Do cardiotoxins possess a functional site? Structural and chemical modification studies reveal the functional site of the cardiotoxin from Naja nigricollis". Biochimie. 72 (8): 575–588. doi:10.1016/0300-9084(90)90121-v. ISSN   0300-9084. PMID   2126462.
  3. Sivaraman, T.; Kumar, T. K. S.; Huang, C. C.; Yu, C. (January 1998). "The role of acetic acid in the prevention of salt-induced aggregation of snake venom cardiotoxins". IUBMB Life. 44 (1): 29–39. doi: 10.1080/15216549800201032 . ISSN   1521-6543. PMID   9503145. S2CID   28326180.
  4. Bhaskaran, Rajagopalan; Huang, Chung Chih; Chang, Ding Kwo; Yu, Chin (1994-01-27). "Cardiotoxin III from the Taiwan Cobra (Naja naja atra): Determination of Structure in Solution and Comparison with Short Neurotoxins". Journal of Molecular Biology. 235 (4): 1291–1301. doi:10.1006/jmbi.1994.1082. ISSN   0022-2836. PMID   8308891.
  5. Su, Shu-Hui; Su, Shu-Jem; Lin, Shinne-Ren; Chang, Kee-Lung (2003-11-15). "Cardiotoxin-III selectively enhances activation-induced apoptosis of human CD8+ T lymphocytes". Toxicology and Applied Pharmacology. 193 (1): 97–105. doi:10.1016/S0041-008X(03)00327-2. ISSN   0041-008X. PMID   14613720.
  6. Lin, Kuei-Li; Su, Jung-Chen; Chien, Ching-Ming; Chuang, Pei-Wen; Chang, Long-Sen; Lin, Shinne-Ren (2010-06-15). "Down-regulation of the JAK2/PI3K-mediated signaling activation is involved in Taiwan cobra cardiotoxin III-induced apoptosis of human breast MDA-MB-231 cancer cells". Toxicon. 55 (7): 1263–1273. doi:10.1016/j.toxicon.2010.01.017. ISSN   0041-0101. PMID   20144642.
  7. Chen, Xingyong; Lv, Ping; Liu, Jing; Xu, Kangsen (2009-07-01). "Apoptosis of human hepatocellular carcinoma cell (HepG2) induced by cardiotoxin III through S-phase arrest". Experimental and Toxicologic Pathology. 61 (4): 307–315. doi:10.1016/j.etp.2008.09.006. ISSN   0940-2993. PMID   18986802.
  8. Chiou, Jing-Ting; Shi, Yi-Jun; Wang, Liang-Jun; Huang, Chia-Hui; Lee, Yuan-Chin; Chang, Long-Sen (September 2019). "Naja atra Cardiotoxin 3 Elicits Autophagy and Apoptosis in U937 Human Leukemia Cells through the Ca2+/PP2A/AMPK Axis". Toxins. 11 (9): 527. doi: 10.3390/toxins11090527 . ISSN   2072-6651. PMC   6784133 . PMID   31547294.