Spermine isolated and identified as the major trypanocidal compound from the snake venom of Eristocophis macmahoni causes autophagy in Trypanosoma brucei

Merkel, Patrick; Beck, Alexander; Muhammad, Khalid; Ali, Syed Abid; Schönfeld, Caroline; Voelter, Wolfgang; Duszenko, Michael

doi:10.1016/j.toxicon.2007.04.022

Cited by 16 publications

(12 citation statements)

References 34 publications

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“…The extensive vacuolization and the presence of cytoplasmic contents inside vacuoles clearly indicate that VIP-induced cell damage has features of autophagic-like death, similar to those observed after nutrient starvation of the cells. 12,13 Moreover, we investigated the presence of the microtubuleassociated protein-1 light-chain-3 (LC3)…”

Section: Resultsmentioning

confidence: 99%

“…The concept of autophagy in trypanosomatids is new and has been mainly related to processes of differentiation and change of stage, 29,30 although recent reports have shown that other antiparasitic drugs could induce autophagy. 13,31 Various studies have recently described the functional involvement of the genes homologous to Atg8 and LC3 in the autophagy of Leishmania major and T. cruzi. 14,32 Although it needs confirmation, their phylogenetic proximity and homology presume a similar functional implication of the Atg8/LC3 ortholog gene Tb07.10C21.40 in T. brucei.…”

Section: Neuropeptides As Endogenous Trypanolytic Factors M Delgado Ementioning

confidence: 99%

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Neuropeptides kill African trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death

et al. 2008

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Trypanosoma brucei is the causative agent of African sleeping sickness. Available treatments are ineffective, toxic and susceptible to resistance by the parasite. Here we show that various endogenous neuropeptides act as potent antitrypanosome agents. Neuropeptides exerted their trypanolytic activity through an unusual mechanism that involves peptide uptake by the parasite, disruption of lysosome integrity and cytosolic accumulation of glycolytic enzymes. This promotes an energetic metabolism failure that initiates an autophagic-like cell death. Neuropeptide-based treatment improved clinical signs in a chronic model of trypanosomiasis by reducing the parasite burden in various target organs. Of physiological importance is the fact that hosts respond to trypanosome infection producing neuropeptides as part of their natural innate defense. From a therapeutic point of view, targeting of intracellular compartments by neuropeptides suppose a new promising strategy for the treatment of trypanosomiasis.

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Section: Resultsmentioning

confidence: 99%

Section: Neuropeptides As Endogenous Trypanolytic Factors M Delgado Ementioning

confidence: 99%

Neuropeptides kill African trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death

et al. 2008

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“…Qualitative identification and quantitation of spermine 17, a linear polyamine, in the viper venom showed that this compound constituted approximately 1% of the dry venom mass [104]. The analysis was carried out on a polymer crosslinked amino column (Grom-SIL 120 Amino-2 PA) with ammonium formate buffer adjusted to pH 3.5 in the aqueous phase.…”

Section: Drug Discoverymentioning

confidence: 99%

The advantages of ESI‐MS detection in conjunction with HILIC mode separations: Fundamentals and applications

Nguyen

Schug²

2008

J of Separation Science

256

133

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The analysis of highly hydrophilic, ionic, and polar compounds has been performed by HILIC-ESI-MS for the last few years. The use of low aqueous/high polar organic solvent content in HILIC separation mobile phase is almost ideal for ESI-MS detection in many cases, resulting in increased sensitivity. Although the addition of modifiers such as acids or salts is necessary in some circumstances for a good separation, the optimum concentrations used are still highly amenable for ESI-MS analysis, showing few deleterious effects. In this review, the mechanism of HILIC separation and ESI ion generation will be briefly discussed, followed by a summary of method development and applications in several fields of research including pharmaceutical, biomolecular, food, metabolic, and environmental analysis.

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“…Interestingly, the amount of purified trimorphin required for 100 % reduction in parasite cell viability corresponded to a mere 3.3 % of the amount of crude venom required to accomplish the same task. Merkel et al (2007) evaluated the activity of the whole venom of the leaf-nosed viper Eristocophis macmahoni, as well as that of the most active venom compound, polyamine spermine, on T. brucei Drug Discovery DOI 10.1007/978-94-007-6726-3_4-1 # Springer Science+Business Media Dordrecht 2015 bloodstream forms. These authors reported IC 50 values of 186 ng/ml and 3.5 mM, for whole venom and spermine, respectively, and showed that the polyamine oxidase activity in the fetal calf serum used for parasite cultivation was responsible for the trypanocidal effect of spermine, whereas the lytic activity of the crude venom was virtually independent from serum.…”

Section: Snake Venomsmentioning

confidence: 99%

Venoms as Sources of Novel Anti-parasitic Agents

Adade

Souto-Padrón

2015

Toxins and Drug Discovery

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Parasitic diseases continue to take an enormous toll on human health, particularly in developing tropical regions, where more than 200 millions people are infected with protozoan parasites belonging to the genera Plasmodium, Trypanosoma, and Leishmania, responsible for Malaria, African trypanosomiasis, and Chagas disease, and the different forms of leishmaniasis. Current antiprotozoan chemotherapeutic agents are toxic and have many decades of clinical use, with ever decreasing efficacy due to drug resistance. Therefore, there is an urgent need for the development of novel agents against protozoan parasites. In recent years, research into animal venom toxins and other molecules isolated from natural sources has intensified, focusing on the potential of these compounds to interfere with parasite physiology and/or vector biology. Venom components and their derivatives already represent more than 50 % of pharmaceuticals in clinical use, and novel drugs to treat parasitic diseases could be developed from these compounds. This chapter examines in detail the research into numerous animal venom toxins with potential to become novel clinical agents to treat protozoan-borne diseases. Also, some of these compounds are capable of inhibiting parasite establishment in the insect vector, representing good candidates to be used in the development of strategies for disease transmission control. Overall, the studies discussed here correspond to significant advances in the discovery of new antiprotozoan molecules, and highlight the potential of venoms and toxins as rich sources of relevant biologically active compounds.

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Spermine isolated and identified as the major trypanocidal compound from the snake venom of Eristocophis macmahoni causes autophagy in Trypanosoma brucei

Cited by 16 publications

References 34 publications

Neuropeptides kill African trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death

Neuropeptides kill African trypanosomes by targeting intracellular compartments and inducing autophagic-like cell death

The advantages of ESI‐MS detection in conjunction with HILIC mode separations: Fundamentals and applications

Venoms as Sources of Novel Anti-parasitic Agents

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