Jararhagin, a snake venom metalloproteinase, induces a specialized form of apoptosis (anoikis) selective to endothelial cells

Tanjoni, Isabelle; Weinlich, Ricardo; Della-Casa, Maisa S.; Clissa, Patrı́cia Bianca; Saldanha-Gama, Roberta; Freitas, Marta Sampaio de; Barja‐Fidalgo, Christina; Amarante-Mendes, Gustavo P.; Moura-da-Silva, Ana Maria

doi:10.1007/s10495-005-2945-1

Cited by 96 publications

(55 citation statements)

References 40 publications

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“…The results indicated an apparent membrane rupture in MDCK cells at the highest concentrations studied ( Figure 1B), showing an increase in LDH release. Apoptosis caused by snake venoms is mediated by various different components, such as metalloprotease, phospholipase A2 and L-amino acid oxidase [4][5][6][7][8]. Several studies have confirmed the involvement of Bothrops and Bothropoides venom components in apoptosis [9,10].…”

Section: Resultsmentioning

confidence: 99%

Cytotoxicity of Bothrops pauloensis Venom on Madin-Darby Canine Kidney Cells: Cell Death Mechanism

Ad¹,

Ico²,

Db³

et al. 2017

J Kidney

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Bothrops is a genus of pit vipers (snakes) endemic to Central and South America. Snake envenomation (Bothrops genus) specifically Bothropoides pauloensis, a venomous snake popularly known as "Jararaca pintada", which is found in the Brazilian territory or more commonly in the southwest of the state of Sao Paulois. Acute kidney injury is one of the complications observed in Bothrops snakebite with relevant morbidity and mortality. Here, we showed the cytotoxic effect of Bothropoides pauloensis venom on MDCK cells, intracellular mitochondrial membrane potentiality (ΔΨm), BpV regulated Reactive Oxygen Species (ROS) and activation of caspases 3 and 7 in MDCK cells. MDCK cells were treated with different concentrations of B. pauloensis venom for 24 hrs and cell death were measured with annexin V and PI staining and detected by flow cytometry. MDCK cells were treated with two different concentrations (IC50 and 2 × IC50) of BpV after 24 hrs. All data are expressed as mean ± SEM of three independent experiments with six replicates (ANOVA and Dunnett test, *p<0.05). Cytotoxicity was assessed by MTT assay and the treatment with BpV caused decrease in cell viability, with an IC50 of 7.5 µg/mL. After the treatment, amounts of ROS in the BpV-treated MDCK-cells (7.5 µg/mL) showed significant right dislocation of the fluorescence peak in the histogram, when compared with the untreated control group. Caspase 3 and 7 activity was determined in presence of the fluorogenic Ac-DEVDafc substrate after treatment with Bothropoides pauloensis venom (12 hrs) then the result indicated apoptotic involvement in BpV-induced cell death. Similar results were also found for venoms of other Bothrops and Bothropoides genus snakes such as B. alternatus, B. insularis and B. leucurus.

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Section: Resultsmentioning

confidence: 99%

Cytotoxicity of Bothrops pauloensis Venom on Madin-Darby Canine Kidney Cells: Cell Death Mechanism

Ad¹,

Ico²,

Db³

et al. 2017

J Kidney

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“…Moreover, apoptosis was dependent on BaP1 catalytic activity. Jarharagin, a PIII SVMP from B. jararaca also induced anoikis in endothelial cells, but had no effect in fibroblasts or murine peritoneal adherent cells (MPAC) (32).…”

Section: Discussionmentioning

confidence: 98%

“…(22) There are several reports on the ability of SVMPs to induce apoptosis in endothelial cells (9,21,32,34,35). BaP1, a PI SVMP from B. asper with weak hemorrhagic activity induced detachment of endothelial cells by proteolysis of matrix components, resulting in anoikis in endothelial cells (9).…”

Section: Discussionmentioning

confidence: 99%

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rACLF, a recombinant snake venom metalloprotease, activates endothelial cells in vitro

Moraes¹,

Fritzen²,

Chudzinski-Tavassi³

et al. 2008

J. Venom. Anim. Toxins incl. Trop. Dis

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“…A recent report described two independent apoptotic mechanisms simultaneously induced by a single stimulus. In the first pathway, there was breakdown of focal adhesion components leading to anoikis, while the second was a direct effect through receptor-mediated signal transduction pathways initiated by a cell adhesion domain (204). Conceivably, this scenario could be occurring during gingipain-induced apoptosis in BCAEC.…”

Section: Caspase-independent P Gingivalis -Induced Apoptosismentioning

confidence: 99%

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

Sheets

Robles-Price²,

McKenzie³

et al. 2008

Front Biosci

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Porphyromonas gingivalis, a major periodontal pathogen, must acquire nutrients from host derived substrates, overcome oxidative stress and subvert the immune system. These activities can be coordinated via the gingipains which represent the most significant virulence factor produced by this organism. In the context of our contribution to this field, we will review the current understanding of gingipain biogenesis, glycosylation, and regulation, as well as discuss their role in oxidative stress resistance and apoptosis. We can postulate a model, in which gingipains may be part of the mechanism for P. gingivalis virulence. KeywordsPorphyromonas gingivalis; gingipains; apoptosis; caspase-independent apoptosis; oxidative stress; VimA; anoikis; N-cadherin; VE-cadherin; integrin β1; VimA; VimE; VimF; DNA repair; glycosylation; virulence; host cell survival; HRgpA; RgpB; Kgp; Review INTRODUCTIONP. gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiological agent of periodontal disease and is also linked to cardiovascular disease and other systemic diseases [reviewed in (43,103)]. The inflammatory nature of periodontal disease implies that innate host defense mechanisms play a vital role in limiting bacterial growth. During active infection including tissue invasion, toxic reactive oxygen metabolites (e.g. superoxides, hydrogen peroxide and hydroxyl radicals) are mostly generated by polymorphonuclear leukocytes and macrophages (27,29). In order to survive in the inflammatory environment of the periodontal pocket, the bacterium must not only obtain nutrients for growth, but also overcome oxidative stress and subvert the immune defense system. Coordinated regulation of these activities would be beneficial to the bacterium. While there is documented evidence of the response of P. gingivalis to environmental stimulus (56,117,126), one possible mechanism for coordination may occur via the gingipains produced by this bacterium. The presence of P. gingivalis in the periodontal pocket and the high levels of gingipain activity detected in gingival crevicular fluid could implicate a role for gingipains in the destruction of the highly vascular periodontal tissue. Protease-associated degradation of cell-cell adhesion proteins on epithelial and endothelial cells resulting in cell death will compromise tissue integrity and facilitate spreading of the bacterium. Furthermore, degradation of the immune response components will facilitate the survival of the organism. Together, these activities may also satisfy the nutritional requirements of the organism. Gingipain-dependent heme accumulation on the bacterium cell surface may also act as an "oxidative sink", thus, leading to protection against oxidative stress (191,193). We will discuss the role of the gingipains in the survival/pathogenicity of P. gingivalis and the unique vim (virulence modulating) locus that is involved in regulation of the gingipains. We will highlight some of our observations that are consistent with the hypothesis that the gingipain...

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Jararhagin, a snake venom metalloproteinase, induces a specialized form of apoptosis (anoikis) selective to endothelial cells

Cited by 96 publications

References 40 publications

Cytotoxicity of Bothrops pauloensis Venom on Madin-Darby Canine Kidney Cells: Cell Death Mechanism

Cytotoxicity of Bothrops pauloensis Venom on Madin-Darby Canine Kidney Cells: Cell Death Mechanism

rACLF, a recombinant snake venom metalloprotease, activates endothelial cells in vitro

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

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