Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom

Long, Chengbo; Liu, Ming; Tian, Huiwen; Li, Ya; Wu, Feilong; Mwangi, James; Lu, Qiumin; El-Aziz, Tarek Mohamed Abd; Lai, Ren; Shen, Chuanbin

doi:10.3390/toxins12120749

Cited by 7 publications

(3 citation statements)

References 67 publications

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“…In the context of CTLs, alboaggregin A was shown to bind strongly with platelet glycoproteins IB and VI, and hence, activated platelet aggregation [ 45 ]. In addition, evidence of enhanced platelet activation and thrombotic microangiopathy-like symptoms has been documented with other related snaclecs [ 46 ]. In terms of CRISPs, the unique pdb|1WVR|A chain A triflin, as well as sp|P0DL18.1|CRVP_OVOOK okinavin from the related hime habu O .…”

Section: Discussionmentioning

confidence: 99%

Proteomics and immunocharacterization of Asian mountain pit viper (Ovophis monticola) venom

et al. 2021

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The venomic profile of Asian mountain pit viper Ovophis monticola is clarified in the present study. Using mass spectrometry-based proteomics, 247 different proteins were identified in crude venom of O. monticola found in Thailand. The most abundant proteins were snake venom metalloproteases (SVMP) (36.8%), snake venom serine proteases (SVSP) (31.1%), and phospholipases A2 (PLA2) (12.1%). Less abundant proteins included L-amino acid oxidase (LAAO) (5.7%), venom nerve growth factor (3.6%), nucleic acid degrading enzymes (3.2%), C-type lectins (CTL) (1.6%), cysteine-rich secretory proteins (CRISP) (1.2%) and disintegrin (1.2%). The immunoreactivity of this viper’s venom to a monovalent antivenom against green pit viper Trimeresurus albolabris, or to a polyvalent antivenom against hemotoxic venom was investigated by indirect ELISA and two-dimensional (2D) immunoblotting. Polyvalent antivenom showed substantially greater reactivity levels than monovalent antivenom. A titer for the monovalent antivenom was over 1:1.28x107 dilution while that of polyvalent antivenom was 1:5.12x107. Of a total of 89 spots comprising 173 proteins, 40 spots of predominantly SVMP, SVSP and PLA2 were specific antigens for antivenoms. The 49 unrecognized spots containing 72 proteins were characterized as non-reactive proteins, and included certain types of CTLs and CRISPs. These neglected venom constituents could limit the effectiveness of antivenom-based therapy currently available for victims of pit viper envenomation.

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Section: Discussionmentioning

confidence: 99%

Proteomics and immunocharacterization of Asian mountain pit viper (Ovophis monticola) venom

et al. 2021

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“…Platelet preparation from wild type (WT) and GPIbα deficient ( GPIbα −/− ) mice were performed as we previously described [ 47 , 51 ]. Platelet aggregation assay was performed as before [ 22 , 52 ]. Animal protocol for this study was reviewed and approved by the Animal Care and Use Committee at Kunming Institute of Zoology, Chinese Academy of Sciences.…”

Section: Methodsmentioning

confidence: 99%

Soy Isoflavones Inhibit Both GPIb-IX Signaling and αIIbβ3 Outside-In Signaling via 14-3-3ζ in Platelet

Liu

Gan

et al. 2021

Molecules

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Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s−1) and high (1800 s−1) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and GPIbα deficient mice. The interaction of these soy isoflavone with 14-3-3ζ was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of αIIbβ3-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s−1). These soy isoflavone interact with 14-3-3ζ and inhibited both GPIb-IX and αIIbβ3-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3ζ is a novel target of genistein and daidzein. 14-3-3ζ, an adaptor protein that regulates both GPIb-IX and αIIbβ3-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition.

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“…Venom samples from wild T. stejnegeri , D. r. siamensis , D. acutus , N. atra , and P. mucrosquamatus snakes were collected in China according to previous study protocols ( 33 , 34 ). The samples were centrifuged at 12,000× g for 10 min at 4°C to remove debris, then lyophilized, and stored at −80°C until use.…”

Section: Methodsmentioning

confidence: 99%

A Strategy for Efficient Preparation of Genus-Specific Diagnostic Antibodies for Snakebites

Long

et al. 2021

Front. Immunol.

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As said by former United Nations Secretary-General Kofi Annan, “Snakebite is the most important tropical disease you’ve never heard of.” Listed as a priority neglected tropical disease by the World Health Organization, snakebite envenoming (SBE) kills in excess of 125,000 people per year. However, due to the complexity and overlap of snake venom compositions, few reliable venom diagnostic methods for genus-/species-specific identification, which is crucial for successful SBE therapy, are available. Here, we develop a strategy to select and prepare genus-specific snake venom antibodies, which allows rapid and efficient clinical diagnosis of snakebite. Multi-omics approaches are used to choose candidate antigens from snake venoms and identify genus-specific antigenic epitope peptide fragments (GSAEPs) with ideal immunogenicity, specificity, and spatial accessibility. Double-antibody sandwich ELISA kit was established by matching a polyclonal antibody against a natural antigen and a monoclonal antibody that was prepared by natural protein as antigen and can specifically target the GSAEPs. The kit shows the ability to accurately identify venoms from similar genera of Trimeresurus and Protobothrops with a detection limit of 6.25 ng/ml on the snake venoms and a little cross-reaction, thus proving high feasibility and applicability.

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Potential Role of Platelet-Activating C-Type Lectin-Like Proteins in Viper Envenomation Induced Thrombotic Microangiopathy Symptom

Cited by 7 publications

References 67 publications

Proteomics and immunocharacterization of Asian mountain pit viper (Ovophis monticola) venom

Proteomics and immunocharacterization of Asian mountain pit viper (Ovophis monticola) venom

Soy Isoflavones Inhibit Both GPIb-IX Signaling and αIIbβ3 Outside-In Signaling via 14-3-3ζ in Platelet

A Strategy for Efficient Preparation of Genus-Specific Diagnostic Antibodies for Snakebites

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