Article

Diamphotoxin. The arrow poison of the !Kung Bushmen.

Journal of Biological Chemistry (Impact Factor: 4.57). 11/1983; 258(19):11924-31.
Source: PubMed

ABSTRACT We have purified the arrow poison extracted from Diamphidia nigro-ornata pupae by the !Kung Bushmen of Southern Africa, and named it diamphotoxin. The toxin is a single chain polypeptide of Mr = 60,000 with an isoelectric point of pH 9.5. It blocks neuromuscular function and is cardiotoxic and hemolytic, and the minimum lethal dose for mice is 25 pg (less than 0.5 fmol). The toxin binds tightly to cells, permitting the resolution of two distinct phases. Erythrocytes exposed to toxin in the absence of divalent cations show no apparent lesion (phase I). After washing and addition of 1 mM Ca2+, there occurs a rapid efflux of K+ followed by the loss of hemoglobin (phase II). The pH optimum for phase I is pH 6.7 and for phase II pH 8.6. The action of the toxin is noncatalytic, requiring a solution concentration of approximately 65 toxin molecules/cell for hemolysis of sheep erythrocytes under standard conditions. Ca2+ ions induce a conformational change in the free, purified toxin molecule. We propose that this change also occurs in membrane-bound toxin. Hemolysis would result from the formation of channels permitting the diffusion of small cations.

0 Followers
 · 
150 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Membrane fractions from homogenized adult Schistosoma mansoni are known to lyse host red blood cells (RBC's), which serve as an important nutrient source for the parasite. In order to learn more about the hemolytic process, we investigated the effects of pH and temperature on the steps involved in the hemolytic process. For maximum schistosome induced hemolysis to occur the worm lytic agent must be in contact with RBCs in a low pH (pH 5.1), high temperature (37 degrees C) environment for a short time (30 min), after which hemolysis occurs at both pH 7.5 and 5.1. At pH 7.5 the hemolytic process is relatively temperature independent and highly concentration dependent. Dose-response experiments suggest that a multi-hit process of hemolysis is probably involved. Temperature and dextran experiments suggest that a pore is formed in the RBC membrane at pH 7.5. At pH 5.1 hemolysis is temperature dependent and not very concentration dependent. Dose-response data suggest that a single-hit process of hemolysis is utilized at low pH. The hemolytic process at pH 7.5, the pH of the host blood, and pH 5.1, the approximate pH of the worm gut, appears to be very different.
    Journal of Experimental Zoology 03/1995; 271(4):315-22. DOI:10.1002/jez.1402710409
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die San oder Buschmänner der Kalahari im südlichen Afrika verwenden seit jeher Larven von auf Commiphora und Sclerocarya lebenden Käfern als Quelle für ihre Pfeilgifte. Es handelt sich dabei um Larven von pflanzenfressenden Blattkäfern (Diamphidia- und Polyclada-Arten) und auf ihnen schmarotzenden, fleischfressenden Laufkäfern (Lebistina-Arten). In den letzten 25 Jahren gelang es, das giftige Prinzip zu isolieren. Das Diamphidiatoxin genannte Toxin erwies sich als ein mit Wasser leicht extrahierbares, hitzeempfindliches, basisches Protein vom Molgewicht 50.000 — 60.000, einem isolelektischen Punkt bei 8, 0 — 9, 5 und hoher Letalität bei Labortieren. Es wirkt sowohl auf rote Blutzellen als auch auf alle erregbaren Zellen. Eine extrem schnelle, massive Hämolyse und die Störung des Eletrolytgleichgewichts stehen im Vordergrund; Neurotoxizität, Krämpfe, Schwäche und Lähmung sind weitere wichtige Aspekte seiner Wirkung. Es bestehen zum Teil noch erhebliche Diskrepanzen in der endgültigen Beurteilung des Giftes. Kokons, Larven, Käfer und Giftpfeile werden in Fotos vorgestellt.
    Biologie in unserer Zeit 04/2004; 34(2):88-94. DOI:10.1002/biuz.200410247
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ‘There are more things between heaven and earth…’ Despite the progress of science during the past four centuries, Shakespeare's words did not lose their actuality. Knowledge about the etiology of diseases is still limited, and for many life-threatening illnesses no effective treatments exist. Nature always has been a valuable source of drugs and, despite the unprecedented opportunities afforded by medicinal chemistry, continues to deliver lead compounds. Traditionally, research on natural sources was focused on terrestrial plants and microorganisms. More recently, however, organisms of marine origin are also being investigated. Here, the possibilities of unconventional and hardly explored sources are discussed.
    Drug Discovery Today 06/2004; 9(10):450-8. DOI:10.1016/S1359-6446(04)03066-1 · 5.96 Impact Factor
Show more

Preview

Download
1 Download
Available from