RESUMEN
Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. CTX III-induced K562 cell apoptosis was confirmed by DNA fragmentation (DNA ladder, sub-G1 formation) and phosphatidylserine (PS) externalization with an IC50 value of 1.7 mug/ml at 48 h. A mechanistic analysis demonstrated that CTX III-induced apoptotic cell death was accompanied by up-regulation of both Bax and endonuclease G (Endo G), and downregulation of Bcl-X(L). CTX III had no effect on the levels of Bcl-2, Bid, XIAP survivin, and AIF proteins. CTX III treatment caused loss of the mitochondrial membrane potential (delta psi m), release of mitochondrial cytochrome c to the cytosol, and activation of both caspase-9 and -3. CTX III-induced apoptosis was significantly blocked by the broad-spectrum caspase inhibitor Z-VAD-FMK. However, CTX III did not generate reactive oxygen species (ROS) and antioxidants, including N-acetylcysteine and catalase, did not block CTX III-induced apoptosis in K562 cells. Modulation of Bax, Bcl-X(L), and the Endo G proteins, release of mitochondrial cytochome c, and activation of caspase-3 and -9 all are involved in the CTX III-triggered apoptotic process in human leukemia K562 cells.
Asunto(s)
Humanos , Proteína bcl-X/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proteínas Mitocondriales/metabolismo , Membranas Mitocondriales/efectos de los fármacos , Potenciales de la Membrana/efectos de los fármacos , Células K562 , Proteínas Inhibidoras de la Apoptosis/metabolismo , Endodesoxirribonucleasas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Proteínas Cardiotóxicas de Elápidos/farmacología , Citocromos c/metabolismo , Proliferación Celular/efectos de los fármacos , Caspasas/metabolismo , Apoptosis/efectos de los fármacosRESUMEN
Hemolytic activity of eight Peruvian snake venoms from the families Viperidae and Elapidae (Bothrops atrox, B. pictus, B. hyoprorus, B. bilineatus, B. neuwedii, Lachesis m. muta, Crotalus d. terrificus, Microrus tschudi), and three Brazilian viperids (B. jararacussu, B. alternatus and C. d. collilineatus) is described. None of the venoms cause direct lysis on washed human erythrocytes. However, all of then caused indirect hemolysis provided that the incubation medium contains an exogenous source of lecithin. Venom of Micrurus tschudi was the most hemolytic (HD50 2.8 ug/ml) while that of B. bilineatus was the least (HD50 681.3 ug/ml). Only six of eleven venoms showed parallel curves of hemolytic activity, and the HD50 varied from 198 to 681 ug/ml and the following decreasing order of hemolytic activity was obtained: L. muta, C. d. terrificus, C. d. collilineatus, B. hyoprorus, B. bilineatus, B. alternatus
Asunto(s)
Humanos , Animales , Hemólisis , Venenos de Víboras/farmacología , Venenos Elapídicos/farmacología , Proteínas Cardiotóxicas de Elápidos/farmacología , Fosfolipasas A/farmacología , Análisis de RegresiónRESUMEN
Trypanosoma cruzi strain Y and clone Dm28c and other trypanosomatids were exposed to two lytic agents, Rhodnius prolixus hemolytic factor (RHF) and mellitin, in vitro. In both cases, the result was a significant decrease in the number of parasites after a 30-min treatment at 37-C. RHF and mellitin had distinct activities on differente strains and species of trypanosomatids. These observations suggest that RHF may be an important factor in selecting resistant strains of trypanosomes for development in the vector's gut