On the interaction of cobra venom protein cardiotoxins with erythrocytes

Zusman, Neil; Miklas, Theodore M.; Graves, T A; Dambach, George; Hudson, Richard

doi:10.1016/0006-291x(84)91601-2

Cited by 10 publications

(3 citation statements)

References 15 publications

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“…In vivo, CTXs cause systolic heart arrest, severe tissue necrosis, and/or blindness of the eye (). In vitro, general cytotoxicity toward many cell types such as human erythrocytes, cancer cells, and cardiomyocytes has been demonstrated ( − ). Depending on the experimental conditions, CTXs have also been shown to induce aggregation, fusion, and membrane leakage of phospholipid vesicles ( − ).…”

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confidence: 99%

Peripheral Binding Mode and Penetration Depth of Cobra Cardiotoxin on Phospholipid Membranes as Studied by a Combined FTIR and Computer Simulation Approach

et al. 2003

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Cobra cardiotoxin, a cytotoxic beta-sheet basic polypeptide, is known to cause membrane leakage in many cells including human erythrocytes. Herein, we demonstrate that the major cobra cardiotoxin from Naja atra, CTX A3, can cause leakage of vesicle contents in phosphatidylglycerol (PG) and phosphatidylserine containing, but not in pure phosphatidylcholine (PC), membrane bilayers. By the combined polarized attenuated total reflection infrared spectroscopy and computer simulation studies, CTX A3 is shown to peripherally bind to both zwitterionic and anionic monolayers in a similar edgewise manner with a tilted angle of approximately 48 +/- 20 degrees between the beta-sheet plane of the CTX molecule and the normal of the membrane surface. The average surface area expansion induced by CTX A3 binding to the PG monolayer, however, is two times larger than that of the PC monolayer as determined by the Langmuir minitrough method. Interaction energy considerations of CTX A3 on neutral and negatively charged membrane surfaces suggests that the electrostatic interaction between anionic lipid and cationic CTXs plays a role in modulating the penetration depth of CTX molecules on the initial peripheral binding mode and reveals a pathway leading to the formation of an inserted mode in negatively charged membrane bilayers.

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confidence: 99%

Peripheral Binding Mode and Penetration Depth of Cobra Cardiotoxin on Phospholipid Membranes as Studied by a Combined FTIR and Computer Simulation Approach

et al. 2003

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“…It is therefore obvious that N1 and N2 have a considerable haemolytic activity. Haemolytic PLA 2 enzymes are widely distributed in elapid venoms and may be responsible for many deaths in medical emergencies due to elapid bites [12,20]. The anticoagulant action of venoms from the elapidae is mainly due to the PLA 2 enzymes [10,18] though there are quite a number of non-PLA2 anticoagulants from the same source [11].…”

Section: Discussionmentioning

confidence: 99%

Purification and activity of two phospholipase enzymes from Naja nigricolis nigricolis reinhardt venom

Abubakar

Nok

Abdurahman

et al. 2003

J Biochem & Molecular Tox

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Two phospholipase enzymes NN1 and NN2 were purified from the venom of Naja nigricolis nigricolis Reinhardt to apparent homogeneity. NN1 was purified by a two-step anion-exchange chromatography on DEAE-cellulose column while NN2 was purified by a combination of anion-exchange chromatography and gel filtration on Sephadex G-150. The enzyme NN1 moved homogenously on acrylamide gel as a monomer with a molecular weight of 65 kDa while NN2 was a dimer of 71 kDa. Both enzymes were clearly separated. Both enzymes hydrolyzed L-alpha-phosphatidyl choline with activities of 345.5 for NN1 and 727.8 micromol min(-1) x mg(-1) for NN2. The dimeric 71-kDa enzyme has a higher haemolytic and anticoagulant activity than the monomeric 65-kDa enzyme. It is apparent that the dimeric enzyme has a more pronounced activity than the monomer has, thus toxic activity may be related to the hydrolysis of phospholipids.

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“…In particular, cardiotoxins act on the host organism by instigating rapid depolarization of skeletal and cardiac muscles. They also produce erythrocyte lysis at much higher concentrations [5,6]. At low concentrations, CTX have a lytic effect on human leukemic T-cells with minimal effects on normal immune cells, including B-cells and T-cells [7,8].…”

Section: Introductionmentioning

confidence: 99%

A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T‐cell lines

Smith

Hinman

2004

J Biochem & Molecular Tox

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L1AD3 is a small cyclic synthetic peptide designed to resemble the first loop of a cobra venom cytotoxin. Instead of inducing membrane disruption similar to that caused by the parent toxin, L1AD3 promotes extensive and unusually rapid apoptosis in leukemic T-cells without making the plasma membrane permeable to small fluorescent dyes. Within 4 h, micromolar concentrations of L1AD3 almost totally inhibit thymidine incorporation, and ATP levels decrease significantly. By contrast, normal human white blood cells are not affected by L1AD3, nor is heart cell function affected by it. If L1AD3 kills by interacting with targets that are different from those of currently applied agents, this peptide, or a derivative of it, could become a useful adjunct for cancer chemotherapy.

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On the interaction of cobra venom protein cardiotoxins with erythrocytes

Cited by 10 publications

References 15 publications

Peripheral Binding Mode and Penetration Depth of Cobra Cardiotoxin on Phospholipid Membranes as Studied by a Combined FTIR and Computer Simulation Approach

Peripheral Binding Mode and Penetration Depth of Cobra Cardiotoxin on Phospholipid Membranes as Studied by a Combined FTIR and Computer Simulation Approach

Purification and activity of two phospholipase enzymes from Naja nigricolis nigricolis reinhardt venom

A cyclic peptide, L1AD3, induces early signs of apoptosis in human leukemic T‐cell lines

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