Programmed cell death in Trypanosoma cruzi induced by Bothrops jararaca venom

Abstract

Cells die through a programmed process or accidental death, know as apoptosis or necrosis, respectively. Bothrops jararaca is a snake whose venom inhibits the growth ofIn multicellular organisms, programmed cell death (PCD), also known as apoptosis, is important to control cell number for proper development and tissue homeostasis, removal of unwanted cells and functional control of the immune, haemopoietic and nervous systems (Welburn et al. 1997). The process of PCD is activated by genetically controlled cell suicide machinery (Ameisen 1996). In vertebrate cells, PCD can be activated by external stimuli (ethanol, reactive oxygen species, and receptor ligands) and internal processes (mitotic catastrophe, replication failures, developmental programmed cell death) (Fröhlich & Madeo 2000). PCD is also a common response to cell stress caused by different toxins (Vaux 2002). Independent of the stimulus, PCD usually involves alteration in the mitochondrial membrane permeability, caspase activation, phosphatidylserine (PS) exposure, nuclear and cytoplasmic condensation, DNA fragmentation and breakage of the cell into apoptotic bodies, which are engulfed by the surrounding cells (Vaux & Strasser 1996). PCD is a process found in virtually all nucleated metazoan cells, and it has been recently associated with several species of unicellular eukaryotes, notably kinetoplastids (Ameisen et al. 1995, Welburn et al. 1996, Moreira et al. 1996 (Picot et al. 1997, Peng et al. 2003, and amitochondrion parasites (Chose et al. 2002, Mariante et al. 2003.Snake venoms have been identified as the richest source of enzymes among poisonous animal, displaying a variety of biological activities (Tan & Ponnudurai 1992). Bothrops jararaca is a snake of the viperidae family, largely distributed in Brazil and responsible for 90% of the ophidian envenomations in humans (Bochner & Struchiner 2003). Trypanosoma cruzi is the agent of Chagas disease affecting 16-18 million people in Latin America. We have previously demonstrated that B. jararaca venom inhibited the growth of epimastigote forms of T. cruzi, causing mitochondrion swelling and kinetoplast disorganization (Gonçalves et al. 2002). Because of the ultrastructural alteration observed in the mitochondrion after venom treatment it was suggested that impairment of this organelle was probably responsible for growth inhibition (Gonçalves et al. 2002). However, how epimastigotes were demising was not analyzed. Thus, the aim of the present work was to identify if PCD or necrosis was being induced in T. cruzi epimastigote forms during B. jararaca venom treatment. MATERIALS AND METHODSParasite and venom -Epimastigote forms of T. cruzi (Y strain) were maintained at 28°C by weekly transfers in liver infusion tryptose (LIT) medium (Camargo 1964) supplemented with 10% fetal bovine serum (FBS). Fourday-old cultured epimastigote forms (mid-log phase) were used for the experiments. 34 34 34 3 4 Cell death by snake venom • Poliana Deolindo et al.Lyophilized B. jararaca venom was purchased from the Instit...

Histology of the gastrointestinal tract from Bothrops jararaca and Crotalus durissus

“…The venom of B. jararaca has been investigated in several studies on cancer therapy (SILVA et al, 1996;SANTOS et al, 2008) and chronic parasitic diseases (DEOLINDO et al, 2005;RICARDI, 2010), as well as in studies on the formulation of diagnostic techniques and antihypertensive drugs (MARSH, 2002), including Captopril ® and, more recently, Evasin ® . In turn, the protein "enpak" (endogenous pain killer), which has an analgesic power nearly 600 times that of morphine, was obtained from the toxin produced by C. durissus (MACHADO et al, 2008), which also has potential antimicrobial action (AGUIAR, 2014), antiviral action (RUSSO et al, 2014), antifungal action (NEVES et al, 2015), immunomodulatory action (ALMEIDA et al, 2015), and antitumor action (RUDD et al, 1994).…”

Cytoskeleton, endoplasmic reticulum and nucleus alterations in CHO-K1 cell line after Crotalus durissus terrificus (South American rattlesnake) venom treatment

“…Crotalus durissus terrificus venom and its components can affect a variety of cell types, including macrophages (9), neutrophils (34), mast cells (8), platelets (7) and cells in culture (14), as well as the function of organs such as the heart (19) and the kidney (22).…”

Venoms as Sources of Novel Anti-parasitic Agents

“…Bregge-Silva et al (2012 reported that the median LD 50 of LmL.A.A.O for T. cruzi trypomastigotes in vitro is above 32 mg/ml. In contrast, Deolindo et al (2005Deolindo et al ( , 2010 reported that the crude venom of B. jararaca triggers an apoptosislike programmed cell death in T. cruzi epimastigotes, and showed the L.A.A.O activity present in the venom was responsible for epimastigote "apoptosis" (Deolindo et al 2010). …”

“…Among their antiprotozoal activity, several papers have been published testing the whole venom and/ or purified molecules, with most reports focusing on L-amino acid oxidases (L.A.A.O) and PLA 2 (Table 5) Deolindo et al (2005) described that the crude venom of B. jararaca triggers a programmed cell death process similar to metazoan apoptosis, in T. cruzi epimastigotes (Table 5). Toxins and Drug Discovery DOI 10.1007/978-94-007-6726-3_4- (Toyama et al 2006), B. jararaca (Ciscotto et al 2009;Deolindo et al 2010 (Table 5).…”