Purification and partial characterization of a novel phosphodiesterase from the venom of Trimeresurus stejnegeri: Inhibition of platelet aggregation

Peng, Liang-You; Xu, Xiao-lei; Shen, Dengke; Zhang, Yan; Song, Jiajia; Yan, Xincheng; Guo, Mingchun

doi:10.1016/j.biochi.2011.05.027

Cited by 23 publications

(24 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In concordance with our results the PDE from Crotalus ruber ruber having molecular mass of 98 kDa exhibited two polypeptide chains with molecular mass of 49 kDa in reducing conditions [35]. As well Peng et al [19] reported that the PDE from T. stejnegeri venom is unique being heterodimer with monomeric molecular mass of 100 kDa. The same phenomenon occurs in the case of VLPDE e the molecular mass 120 kDa of the non-reduced protein changes to 60 kDa in reduced form.…”

Section: Discussionsupporting

confidence: 92%

“…Followed by discovery of restrictases the importance of SVPDE diminished remarkably. Later several papers regarding structural features of SVPDE have been published [17,19,35,36]. The PDE from the venom of Bothrops alternatus showed a single band on SDS-PAGE with molecular mass of 105 kDa in both reduced and nonreduced conditions; so this enzyme is a single chain polypeptide [36].…”

Section: Discussionmentioning

confidence: 99%

“…The biological properties of VLPDE and other snake venom PDEs are slightly different. For example, PDEs from Bothrops jararaca [17] and T. stejnegeri [19] cleave ATP more effectively than ADP, in contrast to VLPDE. The inhibition of platelet aggregation has so far been shown (in addition to VLPDE) only with T. stejnegeri enzyme [19] where the effect on platelets is drastic.…”

Section: Discussionmentioning

confidence: 99%

“…For example, PDEs from Bothrops jararaca [17] and T. stejnegeri [19] cleave ATP more effectively than ADP, in contrast to VLPDE. The inhibition of platelet aggregation has so far been shown (in addition to VLPDE) only with T. stejnegeri enzyme [19] where the effect on platelets is drastic. To make some conclusions about the specificity, the alignment/phylogenetic tree confirms lack of sufficient information about phosphodiesterases from reptiles, especially from snakes.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Phosphodiesterase from Vipera lebetina venom – Structure and characterization

et al. 2014

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Phosphodiesterase from Vipera lebetina venom – Structure and characterization

et al. 2014

View full text Add to dashboard Cite

“…In the process of thrombus formation, platelets adhere to the vascular wall, become activated, release agonists and finally aggregate at the injured vascular site [2,3] . Therefore, antiplatelet agents, including ticlopidine, aspirin and the glycoprotein IIb-IIIa (GPIIb/IIIa) inhibitor tirofiban, are used for the treatment and prevention of cardiovascular thrombotic diseases [4,5] .…”

Section: Introductionmentioning

confidence: 99%

The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling

Wang

et al. 2016

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: Psm2, one of the pyrrolidinoindoline alkaloids isolated from whole Selaginella moellendorffii plants, has shown a potent antiplatelet activity. In this study, we further evaluated the antiplatelet effects of Psm2, and elucidated the underlying mechanisms. Methods: Human platelet aggregation in vitro and rat platelet aggregation ex vivo were investigated. Agonist-induced platelet aggregation was measured using a light transmission aggregometer. The antithrombotic effects of Psm2 were evaluated in arteriovenous shunt thrombosis model in rats. To elucidate the mechanisms underlying the antiplatelet activity of Psm2, ELISAs, Western blotting and molecular docking were performed. The bleeding risk of Psm2 administration was assessed in a mouse tail cutting model, and the cytotoxicity of Psm2 was measured with MTT assay in EA.hy926 cells. Results: Psm2 dose-dependently inhibited human platelet aggregation induced by ADP, U4619, thrombin and collagen with IC 50 values of 0.64, 0.37, 0.35 and 0.87 mg/mL, respectively. Psm2 (1, 3, 10 mg/kg) administered to rats significantly inhibited platelet aggregation ex vivo induced by ADP. Psm2 (1, 3, 10 mg/mL, iv) administered to rats with the A-V shunt dose-dependently decreased the thrombus formation. Psm2 inhibited platelet adhesion to fibrinogen and collagen with IC 50 values of 84.5 and 96.5 mg/mL, respectively, but did not affect the binding of fibrinogen to GPIIb/IIIa. Furthermore, Psm2 inhibited AktSer473 phosphorylation, but did not affect MAPK signaling and Src kinase activation. Molecular docking showed that Psm2 bound to phosphatidylinositol 3-kinase β (PI3Kβ) with a binding free energy of -13.265 kcal/mol. In addition, Psm2 did not cause toxicity in EA.hy926 cells and produced only slight bleeding in a mouse tail cutting model. Conclusion: Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling. Psm2 may be a lead compound or drug candidate that could be developed for the prevention or treatment of thrombotic diseases.

show abstract

Isolation and Characterization of a Novel Antithrombotic Peptide from Enzymatic Hydrolysate of Agkistrodon acutus Venom

Chen

et al. 2015

Int J Pept Res Ther

View full text Add to dashboard Cite

Purification and partial characterization of a novel phosphodiesterase from the venom of Trimeresurus stejnegeri: Inhibition of platelet aggregation

Cited by 23 publications

References 37 publications

Phosphodiesterase from Vipera lebetina venom – Structure and characterization

Phosphodiesterase from Vipera lebetina venom – Structure and characterization

The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling

Isolation and Characterization of a Novel Antithrombotic Peptide from Enzymatic Hydrolysate of Agkistrodon acutus Venom

Contact Info

Product

Resources

About