Proteomic analysis of Bothrops pirajai snake venom and characterization of BpirMP, a new P-I metalloproteinase

Bernardes, Carolina P.; Menaldo, Danilo L.; Camacho, E.; Rosa, José César; Escalante, Teresa; Rucavado, Alexandra; Lomonte, Bruno; Gutiérrez, José Marı́a; Sampaio, Suely Vilela

doi:10.1016/j.jprot.2013.01.021

Cited by 43 publications

(32 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hence, it is likely that, even if type IV collagen is hydrolyzed, epitopes could remain within the BM, whereas laminin degradation products might be easily washed out from this structure. Previous investigations demonstrated the degradation of nidogen by SVMPs on tissue homogenates and on the BM preparation Matrigel in vitro [7,16,17,32]. Conversely, we did not observe a reduction in the immunostaining of nidogen, which may indicate that BaP1 does not degrade nidogen of vascular BM on the isolated cremaster muscle.…”

Section: Discussioncontrasting

confidence: 74%

“…Our observations clearly underscore that these SVMPs alter BM components in microvessels, particularly in capillaries. Previous studies have demonstrated the ability of these and other SVMPs to degrade type IV collagen, laminin and nidogen in different in vivo models [7,16–18,32]. However, since most of these studies used tissue homogenates and wound exudates, the precise origin of the degradation products detected is unknown.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of PI and PIII Snake Venom Haemorrhagic Metalloproteinases on the Microvasculature: A Confocal Microscopy Study on the Mouse Cremaster Muscle

et al. 2016

Self Cite

View full text Add to dashboard Cite

The precise mechanisms by which Snake Venom Metalloproteinases (SVMPs) disrupt the microvasculature and cause haemorrhage have not been completely elucidated, and novel in vivo models are needed. In the present study, we compared the effects induced by BaP1, a PI SVMP isolated from Bothrops asper venom, and CsH1, a PIII SVMP from Crotalus simus venom, on cremaster muscle microvasculature by topical application of the toxins on isolated tissue (i.e., ex vivo model), and by intra-scrotal administration of the toxins (i.e., in vivo model). The whole tissue was fixed and immunostained to visualize the three components of blood vessels by confocal microscopy. In the ex vivo model, BaP1 was able to degrade type IV collagen and laminin from the BM of microvessels. Moreover, both SVMPs degraded type IV collagen from the BM in capillaries to a higher extent than in PCV and arterioles. CsH1 had a stronger effect on type IV collagen than BaP1. In the in vivo model, the effect of BaP1 on type IV collagen was widespread to the BM of arterioles and PCV. On the other hand, BaP1 was able to disrupt the endothelial barrier in PCV and to increase vascular permeability. Moreover, this toxin increased the size of gaps between pericytes in PCV and created new gaps between smooth muscle cells in arterioles in ex vivo conditions. These effects were not observed in the case of CsH1. In conclusion, our findings demonstrate that both SVMPs degrade type IV collagen from the BM in capillaries in vivo. Moreover, while the action of CsH1 is more directed to the BM of microvessels, the effects of BaP1 are widespread to other microvascular components. This study provides new insights in the mechanism of haemorrhage and other pathological effects induced by these toxins.

show abstract

Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Effects of PI and PIII Snake Venom Haemorrhagic Metalloproteinases on the Microvasculature: A Confocal Microscopy Study on the Mouse Cremaster Muscle

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…, BmooMPalfa-I from B. moojeni (accession number: P85314) [38], based on a partial sequence obtained by trypsin digestion and mass spectrometry. Recently, it was isolated from the B. pirajai venom a new P1-class metalloproteinase with fibrin(ogen)olytic and thrombolytic activities [39], whose identity with the C-SVMP still needs further analysis, once the internal sequences obtained are similar to others P-I SVMP from Bothops spp. Despite the high similarity between those SVMP, they might act in specific substrates.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous biological activities are attributed to P-I class SVMPs in the context of the envenoming pathology, such as fibrinolysis and fibrinogenolysis, hemorrhage, myonecrosis, inflammation, apoptosis and prothrombin activation in addition to inhibition of platelet aggregation activities [34]–[39]. However, the effect on the complement system has not been investigated.…”

Section: Discussionmentioning

confidence: 99%

P-I Snake Venom Metalloproteinase Is Able to Activate the Complement System by Direct Cleavage of Central Components of the Cascade

et al. 2013

View full text Add to dashboard Cite

BackgroundSnake Venom Metalloproteinases (SVMPs) are amongst the key enzymes that contribute to the high toxicity of snake venom. We have recently shown that snake venoms from the Bothrops genus activate the Complement system (C) by promoting direct cleavage of C-components and generating anaphylatoxins, thereby contributing to the pathology and spread of the venom. The aim of the present study was to isolate and characterize the C-activating protease from Bothrops pirajai venom.ResultsUsing two gel-filtration chromatography steps, a metalloproteinase of 23 kDa that activates Complement was isolated from Bothrops pirajai venom. The mass spectrometric identification of this protein, named here as C-SVMP, revealed peptides that matched sequences from the P-I class of SVMPs. C-SVMP activated the alternative, classical and lectin C-pathways by cleaving the α-chain of C3, C4 and C5, thereby generating anaphylatoxins C3a, C4a and C5a. In vivo, C-SVMP induced consumption of murine complement components, most likely by activation of the pathways and/or by direct cleavage of C3, leading to a reduction of serum lytic activity.ConclusionWe show here that a P-I metalloproteinase from Bothrops pirajai snake venom activated the Complement system by direct cleavage of the central C-components, i.e., C3, C4 and C5, thereby generating biologically active fragments, such as anaphylatoxins, and by cleaving the C1-Inhibitor, which may affect Complement activation control. These results suggest that direct complement activation by SVMPs may play a role in the progression of symptoms that follow envenomation.

show abstract

“…Driven by changes in ecological niche, rapid amino acid sequence divergence within restricted protein families resulted in the selection and inheritance of 'toxin genes' with diverse functions adapted for prey immobilizing, killing and digestion. This leads to the great diversity of snake venom toxins; nonetheless, conserved sequence homology within restricted protein families of venom enable the current sequencing technologies and data mining to identify an unknown toxic gene/protein at high throughput scale (Angulo et al, 2008;Calvete et al, 2009;Fern andez et al, 2010;Corrêa-Netto et al, 2011;Bernardes et al, 2013). The advancement as such in the field of toxinology is promising for a number of reasons: (1) the provision of deeper insights into envenomation pathophysiology; (2) the optimization of antivenom formulation; (3) the development of drug discovery from toxin; (4) the revision of an updated, robust snake systematics.…”

Section: Introductionmentioning

confidence: 99%

Proteomic investigation of Sri Lankan hump-nosed pit viper (Hypnale hypnale) venom

Tan

Sim

et al. 2015

Toxicon

View full text Add to dashboard Cite

Proteomic analysis of Bothrops pirajai snake venom and characterization of BpirMP, a new P-I metalloproteinase

Cited by 43 publications

References 77 publications

Effects of PI and PIII Snake Venom Haemorrhagic Metalloproteinases on the Microvasculature: A Confocal Microscopy Study on the Mouse Cremaster Muscle

Effects of PI and PIII Snake Venom Haemorrhagic Metalloproteinases on the Microvasculature: A Confocal Microscopy Study on the Mouse Cremaster Muscle

P-I Snake Venom Metalloproteinase Is Able to Activate the Complement System by Direct Cleavage of Central Components of the Cascade

Proteomic investigation of Sri Lankan hump-nosed pit viper (Hypnale hypnale) venom

Contact Info

Product

Resources

About