Background: Beta-cardiotoxin (β-CTX), the three-finger toxin isolated from king cobra () venom, possesses β-blocker activity as indicated by its negative chronotropy and its binding property to both β-1 and β-2 adrenergic receptors and has been proposed as a novel β-blocker candidate. Previously, β-CTX was isolated and purified by FPLC. Here, we present an alternative method to purify this toxin. In addition, we tested its cytotoxicity against different mammalian muscle cell types and determined the impact on cardiac function in isolated cardiac myocyte so as to provide insights into the pharmacological action of this protein.
Methods: β-CTX was isolated from the crude venom of the Thai king cobra using reverse-phased and cation exchange HPLC. cellular viability MTT assays were performed on mouse myoblast (C2C12), rat smooth muscle (A7r5), and rat cardiac myoblast (H9c2) cells. Cell shortening and calcium transient dynamics were recorded on isolated rat cardiac myocytes over a range of β-CTX concentration.
Results: Purified β-CTX was recovered from crude venom (0.53% w/w). MTT assays revealed 50% cytotoxicity on A7r5 cells at 9.41 ± 1.14 µM (n = 3), but no cytotoxicity on C2C12 and H9c2 cells up to 114.09 µM. β-CTX suppressed the extend of rat cardiac cell shortening in a dose-dependent manner; the half-maximal inhibition concentration was 95.97 ± 50.10 nM (n = 3). In addition, the rates of cell shortening and re-lengthening were decreased in β-CTX treated myocytes concomitant with a prolongation of the intracellular calcium transient decay, indicating depression of cardiac contractility secondary to altered cardiac calcium homeostasis.
Conclusion: We present an alternative purification method for β-CTX from king cobra venom. We reveal cytotoxicity towards smooth muscle and depression of cardiac contractility by this protein. These data are useful to aid future development of pharmacological agents derived from β-CTX.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375408 | PMC |
http://dx.doi.org/10.1590/1678-9199-JVATITD-2020-0005 | DOI Listing |
Toxins (Basel)
December 2024
National Natural Toxins Research Center (NNTRC), Texas A&M University-Kingsville, Kingsville, TX 78363, USA.
King cobra () venom comprises a diverse array of proteins and peptides. However, the roles and properties of these individual components are still not fully understood. Among these, Cysteine-rich secretory proteins (CRiSPs) are recognized but not fully characterized.
View Article and Find Full Text PDFCureus
November 2024
Department of Emergency and Hospital Medicine, Division of Medical Toxicology, Lehigh Valley Health Network/University of South Florida Morsani College of Medicine, Allentown, USA.
Non-native snake envenomations can be difficult to manage because of challenges obtaining appropriate antivenom and unfamiliarity with the expected clinical effects. This case report describes a 37-year-old man who was envenomated by his pet monocled cobra (). He experienced respiratory failure, requiring intubation and mechanical ventilation.
View Article and Find Full Text PDFEast Mediterr Health J
September 2024
Department of Emergency Medicine, School of Medicine, Emory University, USA.
Background: Snakebite envenomation remains a significant public health concern in Asir Province of Saudi Arabia.
Aim: To characterize snake species and the clinical presentation, outcome and management of snakebite cases admitted to 4 major hospitals in Asir Province, Saudi Arabia .
Methods: This retrospective study reviewed medical records of paediatric and adult snakebite cases admitted to 4 regional hospitals in Saudi Arabia between January 2000 and December 2021 using search terms "snakebite", "cobra", "polyvalent antivenin", "antivenom", "compartment syndrome", and "fasciotomy".
Toxicon
November 2024
School of Science, Monash University Malaysia, Bandar Sunway, Malaysia. Electronic address:
Environ Sci Pollut Res Int
October 2024
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!