Cytotoxic effects of crotamine are mediated through lysosomal membrane permeabilization

Hayashi, Mirian A. F.; Nascimento, Fábio D.; Kerkis, Alexandre; Oliveira, Vitor; Oliveira, Eduardo B.; Pereira, Alexandre da Costa; Rádis‐Baptista, Gandhi; Nader, Helena B.; Yamane, Toshimi; Kerkis, Irina; Tersariol, Ivarne L.S.

doi:10.1016/j.toxicon.2008.06.029

Cited by 82 publications

(91 citation statements)

References 43 publications

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“…Accordingly, many of them strongly induce LCD, including Bacillus anthracis toxin (Newman et al, 2009), Streptomyces hygroscopicus nigericin (Hentze et al, 2003), Pseudomonas aeruginosa pyocyanin (Prince et al, 2008) and Aggregatibacter actinomycetemcomitans leukotoxin (DiFranco et al, 2012). Similarly, the cytotoxicity of enniatin mycotoxins (Ivanova et al, 2012), and venom toxins from cobra (Feofanov et al, 2005) and South American rattlesnake (Hayashi et al, 2008), have been connected with LMP. Additionally, Vibrio parahaemolyticus VepA was recently identified as a new type of LMP-inducing protein (Matsuda et al, 2012).…”

Section: Bacterial Fungal and Snake Toxinsmentioning

confidence: 99%

Lysosomal cell death at a glance

Aits

Jäättelä

2013

Journal of Cell Science

512

417

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Summary Lysosomes serve as the cellular recycling centre and are filled with numerous hydrolases that can degrade most cellular macromolecules. Lysosomal membrane permeabilization and the consequent leakage of the lysosomal content into the cytosol leads to so-called “lysosomal cell death”. This form of cell death is mainly carried out by the lysosomal cathepsin proteases and can have necrotic, apoptotic or apoptosis-like features depending on the extent of the leakage and the cellular context. This article summarizes our current knowledge on lysosomal cell death with an emphasis on the upstream mechanisms that lead to lysosomal membrane permeabilization.

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Section: Bacterial Fungal and Snake Toxinsmentioning

confidence: 99%

Lysosomal cell death at a glance

Aits

Jäättelä

2013

Journal of Cell Science

512

417

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“…Other stimuli, such as various toxins, for example, the lethal toxin from Bacillus anthracis (Averette et al 2009), leukotoxin from the oral bacterium Aggregatibacter actinomycetemcomitans (DiFranco et al 2012), cytotoxins from cobra venom (Feofanov et al 2005), and even crotamine, one of the toxic components of the rattlesnake Crotalus durissus terrificus venom, were also shown to induce LMP, leading to apoptosis (Hayashi et al 2008). It is worth mentioning that the cytotoxicity of various natural compounds toward cancer cells is being investigated more intensively and is considered a very promising approach in combating cancer.…”

Section: Lysosomes In Apoptosismentioning

confidence: 99%

The Endolysosomal System in Cell Death and Survival

Repnik

Česen

Turk

2013

Cold Spring Harbor Perspectives in Biology

114

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The endocytic pathway is a system specialized for the uptake of compounds from the cell microenvironment for their degradation. It contains an arsenal of hydrolases, including proteases, which are normally enclosed in membrane-bound organelles, but if released to the cytosol can initiate apoptosis signaling pathways. Endogenous and exogenous compounds have been identified that can mediate destabilization of lysosomal membranes, and it was shown that lysosomal proteases are not only able to initiate apoptotic signaling but can also amplify the apoptotic pathways initiated in other cellular compartments. The endocytic pathway also receives cargo destined for degradation via the autophagic pathway. By recycling energy and biosynthetic substrates, and by degrading damaged organelles and molecules, the endocytic system assists the autophagic system in resisting apoptotic stimuli. Steps leading to lysosomal membrane permeabilization and subsequent triggering of cell death as well as the therapeutic potential of intervention in lysosomal membrane permeabilization will be discussed.

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“…The determination of cysteine proteases activity in the cytosol to estimate the lysosomal leakage of these enzymes was performed as described by Hayashi et al (2008). Lymphocytes were incubated with 0.001% saponin detergent for 30 min to analyze the proteolytic activity in the cytosol, and an aliquot without incubation with saponin was used as a control to …”

Section: Cytosolic Cysteine Proteases Assaymentioning

confidence: 99%

Evidence of lysosomal membrane permeabilization in mucopolysaccharidosis type I: Rupture of calcium and proton homeostasis

Pereira

Gazarini

RODRIGUES

et al. 2010

Journal Cellular Physiology

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Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of alpha-iduronidase (IDUA), which leads to intralysosomal accumulation of glysosaminoglycans. Patients with MPS I present a wide range of clinical manifestations, but the mechanisms by which these alterations occur are still not fully understood. Genotype-phenotype correlations have not been well established for MPS I; hence, it is likely that secondary and tertiary alterations in cellular metabolism and signaling may contribute to the physiopathology of the disease. The aim of this study was to analyze Ca(2+) and H(+) homeostasis, lysosomal leakage of cysteine proteases, and apoptosis in a murine model of MPS I. After exposition to specific drugs, cells from Idua-/- mice were shown to release more Ca(2+) from the lysosomes and endoplasmic reticulum than Idua+/+ control mice, suggesting a higher intraorganelle store of this ion. A lower content of H(+) in the lysosomes and in the cytosol was found in cells from Idua-/- mice, suggesting an alteration of pH homeostasis. In addition, Idua-/- cells presented a higher activity of cysteine proteases in the cytosol and an increased rate of apoptotic cells when compared to the control group, indicating that lysosomal membrane permeabilization might occur in this model. Altogether, our results suggest that secondary alterations-as changes in Ca(2+) and H(+) homeostasis and lysosomal membrane permeabilization-may contribute for cellular damage and death in the physiopathology of MPS I.

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Cytotoxic effects of crotamine are mediated through lysosomal membrane permeabilization

Cited by 82 publications

References 43 publications

Lysosomal cell death at a glance

Lysosomal cell death at a glance

The Endolysosomal System in Cell Death and Survival

Evidence of lysosomal membrane permeabilization in mucopolysaccharidosis type I: Rupture of calcium and proton homeostasis

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