Purification and biochemical characterization of a novel hemorrhagic metalloproteinase from horned viper (Cerastes cerastes) venom

Boukhalfa-Abib, Hinda; Meksem, Ahmed; Laraba-Djebari, Fatima

doi:10.1016/j.cbpc.2009.05.008

Cited by 20 publications

(11 citation statements)

References 34 publications

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“…In this study, we have shown that injections of Cc or Mm venoms induce myonecrosis in skeletal muscles, which most likely was the result of myotoxin's direct action and hemorragin's indirect action. In muscle tissue, the myonecrosis induced a reduction of the serum CPK concentration (25).…”

Section: Discussionmentioning

confidence: 97%

General characterization of venom from the Moroccan snakes Macrovipera mauritanica and Cerastes cerastes

Oukkache¹,

Lalaoui²,

Ghalim³

2012

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

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Abstract:Ophidian envenomation accidents constitute a serious public health problem in many countries around the globe. Over 5 million such accident cases occur each year causing more than 100,000 deaths. In Africa, more than 20,000 deaths per year are registered while 400,000 envenomation victims retain severe and permanent functional sequelae. In Morocco, snakebites are frequent and of greater severity in children. They occur mostly in rural areas. The incidence of these bites remains poorly understood and vastly underestimated. The epidemiological data are not well known due to the absence of a national registry, whereas a significant proportion of envenomations receive only traditional treatment methods in nonmedical intensive care. This prompted us to investigate the enzymatic and biological properties of venom biochemical constituents from two of the most dangerous snake venoms in Morocco: Cerastes cerastes (Cc) and Macrovipera mauritanica (Mm). Also, we studied the immune cross-reactivity of Cc and Mm venoms in comparison to that of another important dangerous Moroccan viper, Bitis arietans (Ba), to identify the best candidates (venom or a mixture of venoms) for producing the most efficient and protective antivenom. In the present study, we report a preliminary venom characterization of Cc and Mm and the cross-reactivity that may exist between their venoms and Ba. These venoms are known to be highly toxic and contain several proteins that differ by molecular weights. Interestingly, both Cc and Mm venoms are characterized by intense hemorrhagic and phospholipase A 2 activities and their ability to degrade the α and γ chains of fibrinogen. They display very low proteolysis through the casein test. After injection into mice, Cc and Mm induce myonecrosis in skeletal muscles, which most likely reflects direct action of myotoxins and indirect action of hemorrhagic molecules present in these venoms. In mice, this myonecrosis diminishes serum creatine phosphokinase (CPK) levels. As expected, Cc venom is immunogenic and induces highly protective antivenom against Mm and Ba venom antigens. This protective capacity is similar to that of the antivenom produced against the Mm venom.

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Section: Discussionmentioning

confidence: 97%

General characterization of venom from the Moroccan snakes Macrovipera mauritanica and Cerastes cerastes

Oukkache¹,

Lalaoui²,

Ghalim³

2012

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

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“…Most of these proteins act on blood coagulation, including PLA2, the thrombin-like enzymes RP34 and afaâcytin, anticoagulant protease fraction, aggregant serine protease, hemorrhagic metalloproteinase CcH1, and the non-hemorrhagic metalloproteinase CCSV-MPase [11,12,31-35]. In this paper, we report pharmacological activity of biomolecules isolated from Cerastes cerastes on hemostasis process.…”

Section: Reviewmentioning

confidence: 99%

Isolated biomolecules of pharmacological interest in hemostasis from Cerastes cerastes venom

Chérifi

Laraba-Djebari

2013

Journal of Venomous Animals and Toxins including Tropical Disea

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Biomolecules from Cerastes cerastes venom have been purified and characterized. Two phospholipases isolated from Cerastes cerastes venom share 51% of homology. CC2-PLA2 exhibits antiplatelet activity that blocks coagulation. CCSV-MPase, a non-hemorrhagic Zn2+-metalloproteinase, significantly reduced the plasmatic fibrinogen level and hydrolyzes only its Bβ chain. Serine proteinases such as RP34, afaâcytin and CC3-SPase hydrolyze the fibrinogen and are respectively α, αβ and αβ fibrinogenases. In deficient human plasma, afaâcytin replaces the missing factors VIII and IX, and activates purified human factor X into factor Xa. It releases serotonin from platelets and directly aggregates human (but not rabbit) blood platelets. RP34 proteinase also had no effect on both human and rabbit blood platelet aggregation. CC3-SPase revealed a pro-coagulant activity. However, the insolubility of the obtained clot indicates that CC3-SPase does not activate factor XIII. In addition, CC3-SPase clotting activity was carried out with human plasmas from volunteer patients deficient in clotting factors. Results showed that CC3-SPase shortens clotting time of plasma deficient in factors II and VII but with weaker clotting than normal plasma. The clotting time of plasma deficient in factor II is similar to that obtained with normal plasma; suggesting that CC3-SPase is able to replace both factors IIa and VII in the coagulation cascade and thus could be involved in the blood clotting process via an extrinsic pathway. These results imply that CC3-SPase and afaâcytin could repair hemostatic abnormalities and may replace some factors missing in pathological deficiency. Afaâcytin also exhibits α fibrinase property similar to a plasmin-like proteinase. Despite its thrombin-like characteristics, afaâcytin is not inhibited by plasmatic thrombin inhibitors. The procoagulant properties of afaâcytin might have potential clinical applications.

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“…Although many papers on the effect of C. cerastes venom fractions have been published (Daoud et al, 1986;Basheer et al, 1995;Laraba-Djebari et al, 1995;Marrakchi et al, 1995Marrakchi et al, , 1997Abu-Sinna et al, 2003;Boukhalfa-Abib et al, 2009;Chérifi et al, 2010), yet post-synaptic neurotoxins are among the poorly-studied venom fractions of vipers. To our knowledge, the current study reports for the first time the ultrastructural toxic effects produced in the diaphragm of sub-lethally intoxicated mice, by the post-synaptic neurotoxin isolated from the Egyptian sand viper, C. cerastes cerastes.…”

Section: Discussionmentioning

confidence: 99%

Grape seed extract neutralizes the effects of Cerastes cerastes cerastes post-synaptic neurotoxin in mouse diaphragm

Mahmoud

2013

Micron

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Purification and biochemical characterization of a novel hemorrhagic metalloproteinase from horned viper (Cerastes cerastes) venom

Cited by 20 publications

References 34 publications

General characterization of venom from the Moroccan snakes Macrovipera mauritanica and Cerastes cerastes

General characterization of venom from the Moroccan snakes Macrovipera mauritanica and Cerastes cerastes

Isolated biomolecules of pharmacological interest in hemostasis from Cerastes cerastes venom

Grape seed extract neutralizes the effects of Cerastes cerastes cerastes post-synaptic neurotoxin in mouse diaphragm

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