Qiumin Lu

Publications (9)23.1 Total impact

• Article: A novel natriuretic peptide from the cobra venom.

  Yong Zhang, Jianbo Wu, Guoyu Yu, Zhongming Chen, Xingding Zhou, Shaowen Zhu, Rui Li, Yun Zhang, Qiumin Lu
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  ABSTRACT: Natriuretic peptides (NPs) play crucial roles in human physiology and pathophysiology through natriuresis, dieresis and vasorelaxation. NPs are also one of the important components of snake venoms. However, the low abundance in snake venom hampered the investigation. Here, a novel natriuretic peptide named Na-NP was purified from the cobra Naja atra venom. Na-NP consists of 45 amino acid residues and its molecular weight is 4618.5 Da. A full-length cDNA encoding Na-NP was obtained from the cDNA library constructed from the venom gland. The open reading frame of cloned Na-NP was composed of 498bp and coded for a 165-amino acid residue protein precursor. The nucleotide and deduced protein sequences of Na-NP were remarkably conserved with other elapid NPs while significant different from the viperid NPs. Na-NP showed weak activity to relax the aortic rings precontracted with phenylephrine. Meanwhile, Na-NP showed cGMP-promotion activity against primary cultured rabbit endocardial endothelial cells, but had no effect on human platelet aggregation. In conclusion, this is the first report of a natriuretic peptide from the cobra N. atra venom. Na-NP might be served as a useful tool for the study of human NPs and the development of novel therapeutic drugs.
  Toxicon 11/2010; 57(1):134-40. · 2.51 Impact Factor
• Article: SNAKE VENOM C-TYPE LECTINS INTERACTING WITH PLATELET RECEPTORS

  Qiumin Lu, Jeannine M. Clemetson, Kenneth J. Clemetson
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  ABSTRACT: Based on sequence comparison, snake venom components affecting hemostasis have been classified into various families, including serine proteases, metalloproteinases, C-type lectins, disintegrins, and phospholipases. These proteins affect platelet function by binding or degrading von Willebrand factor (VWF) or platelet membrane glycoproteins, activating protease-activated receptors, or modulating ADP release and thromboxane A2 formation. Many snake venom C-type lectins have now been characterized, mostly heterodime ric structures with α and β subunits that are often multimerized to form large molecules. They affect platelet activation by binding to VWF or to specific collagen receptors such as GPIb, α2β1, and GPVI. While simple heterodimeric GPIb-binding molecules mostly inhibit platelet functions, multimeric ones often activate platelets. Some act by inducing VWF to bind to GPIb. Another series of snake venom C-type lectins activates platelets by binding to GPVI, while yet another series affects, platelet function via integrin α2β 1. Snake venom C-type lectins, have a typical fold structure like that in classic C-type lectins, such as the selectins and mannose-binding proteins. More and more structures of these proteins, often complexed with their ligands, have been determined, and structure–activity studies have shown that these proteins are quite a complex group, though with similar backbone folding. Recent studies have shown that snake C-type lectins often interact with more than one platelet receptor and have complex mechanisms of action. It is also noteworthy that snake C-type lectins may act differently in vivo and in vitro.
  10/2008; 26(1):77-93.
• Article: A unique group of inactive serine protease homologues from snake venom.

  Jianbo Wu, Yang Jin, Shurong Zhong, Runqiang Chen, Shaowen Zhu, Wanyu Wang, Qiumin Lu, Yuliang Xiong
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  ABSTRACT: A number of inactive serine protease homologues (SPHs), which have poorly understood functions, have been identified in invertebrates and vertebrates. Recently, several SPH transcripts have been reported from snake venom glands, which provide potential new tools for the study of the functions of SPHs. Herein we report for the first time a snake venom serine protease homologue (svSPH) protein, designated as TjsvSPH, isolated from the venom of Trimeresurus jerdonii. Despite its high sequence similarity to snake venom serine proteases (SVSPs), TjsvSPH is devoid of arginine esterase and proteolytic activity. This is probably due to the replacement of Arg-43 by His-43 in the catalytic triad. TjsvSPH did not influence the coagulation time of human plasma, induce human platelet aggregation, inhibit adenosine diphosphate/thrombin-induced human platelet aggregation or increase capillary permeability. Phylogenetic analysis showed that svSPHs were separated from SVSPs and formed an independent group. Structural analysis revealed that the structures of svSPHs are quite different from those of SPHs previously reported. These results indicate that snake venoms contain a unique group of svSPH proteins.
  Toxicon 07/2008; 52(2):277-84. · 2.51 Impact Factor
• Source

  Available from: abbs.info

  Article: L-amino acid oxidase from Naja atra venom activates and binds to human platelets.

  Rui Li, Shaowen Zhu, Jianbo Wu, Wanyu Wang, Qiumin Lu, Kenneth J Clemetson
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  ABSTRACT: An L-amino acid oxidase (LAAO), NA-LAAO, was purified from the venom of Naja atra. Its N-terminal sequence shows great similarity with LAAOs from other snake venoms. NA-LAAO dose-dependently induced aggregation of washed human platelets. However, it had no activity on platelets in platelet-rich plasma. A low concentration of NA-LAAO greatly promoted the effect of hydrogen peroxide, whereas hydrogen peroxide itself had little activation effect on platelets. NA-LAAO induced tyrosine phosphorylation of a number of platelet proteins including Src kinase, spleen tyrosine kinase, and phospholipase Cgamma2. Unlike convulxin, Fc receptor gamma chain and T lymphocyte adapter protein are not phosphorylated in NA-LAAO-activated platelets, suggesting an activation mechanism different from the glycoprotein VI pathway. Catalase inhibited the platelet aggregation and platelet protein phosphorylation induced by NA-LAAO. NA-LAAO bound to fixed platelets as well as to platelet lysates of Western blots. Furthermore, affinity chromatography of platelet proteins on an NA-LAAO-Sepharose 4B column isolated a few platelet membrane proteins, suggesting that binding of NA-LAAO to the platelet membrane might play a role in its action on platelets.
  Acta Biochimica et Biophysica Sinica 02/2008; 40(1):19-26. · 1.38 Impact Factor
• Article: Snake venom proteins affecting platelets and their applications to anti-thrombotic research.

  Kenneth J Clemetson, Qiumin Lu, Jeannine M Clemetson
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  ABSTRACT: Snake venoms are very complex mixtures of biologically active proteins and peptides that may affect hemostasis in many ways, by activating or inhibiting coagulant factors or platelets, or by disrupting endothelium. They have been classified into various families, including serine proteases, metalloproteinases, C-type lectins, disintegrins and phospholipases. The various members of a particular family act selectively on different blood coagulation factors, blood cells or tissues. Venom proteins affect platelet function in particular by binding to and blocking or clustering and activating receptors or by cleaving receptors or von Willebrand factor. They may also activate protease-activated receptors or modulate ADP release or thromboxane A(2) formation. L-amino acid oxidases activate platelets by producing H(2)O(2). Many of these purified components are valuable tools in platelet research, providing new information about receptor function and signaling.
  Current pharmaceutical design 02/2007; 13(28):2887-92. · 4.41 Impact Factor
• Article: Snake venom C-type lectins interacting with platelet receptors. Structure-function relationships and effects on haemostasis.

  Qiumin Lu, Alexey Navdaev, Jeannine M Clemetson, Kenneth J Clemetson
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  ABSTRACT: Snake venoms contain components that affect the prey either by neurotoxic or haemorrhagic effects. The latter category affect haemostasis either by inhibiting or activating platelets or coagulation factors. They fall into several types based upon structure and mode of action. A major class is the snake C-type lectins or C-type lectin-like family which shows a typical folding like that in classic C-type lectins such as the selectins and mannose-binding proteins. Those in snake venoms are mostly based on a heterodimeric structure with two subunits alpha and beta, which are often oligomerized to form larger molecules. Simple heterodimeric members of this family have been shown to inhibit platelet functions by binding to GPIb but others activate platelets via the same receptor. Some that act via GPIb do so by inducing von Willebrand factor to bind to it. Another series of snake C-type lectins activate platelets by binding to GPVI while yet another series uses the integrin alpha(2)beta(1) to affect platelet function. The structure of more and more of these C-type lectins have now been, and are being, determined, often together with their ligands, casting light on binding sites and mechanisms. In addition, it is relatively easy to model the structure of the C-type lectins if the primary structure is known. These studies have shown that these proteins are quite a complex group, often with more than one platelet receptor as ligand and although superficially some appear to act as inhibitors, in fact most function by inducing thrombocytopenia by various routes. The relationship between structure and function in this group of venom proteins will be discussed.
  Toxicon 07/2005; 45(8):1089-98. · 2.51 Impact Factor
• Article: Snake C-type lectin-like proteins and platelet receptors.

  Kenneth J Clemetson, Qiumin Lu, Jeannine M Clemetson
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  ABSTRACT: Snake venoms are complex mixtures of biologically active proteins and peptides. Many affect haemostasis by activating or inhibiting coagulant factors or platelets, or by disrupting endothelium. Snake venom components are classified into various families, such as serine proteases, metalloproteinases, C-type lectin-like proteins, disintegrins and phospholipases. Snake venom C-type lectin-like proteins have a typical fold resembling that in classic C-type lectins such as the selectins and mannose-binding proteins. Many snake venom C-type lectin-like proteins have now been characterized, as heterodimeric structures with alpha and beta subunits that often form large molecules by multimerization. They activate platelets by binding to VWF or specific receptors such as GPIb, alpha2beta1 and GPVI. Simple heterodimeric GPIb-binding molecules mainly inhibit platelet functions, whereas multimeric ones activate platelets. A series of tetrameric snake venom C-type lectin-like proteins activates platelets by binding to GPVI while another series affects platelet function via integrin alpha2beta1. Some act by inducing VWF to bind to GPIb. Many structures of these proteins, often complexed with their ligands, have been determined. Structure-activity studies show that these proteins are quite complex despite similar backbone folding. Snake C-type lectin-like proteins often interact with more than one platelet receptor and have complex mechanisms of action.
  Pathophysiology of Haemostasis and Thrombosis 02/2005; 34(4-5):150-5. · 2.23 Impact Factor
• Article: GPIb is involved in platelet aggregation induced by mucetin, a snake C-type lectin protein from Chinese habu (Trimeresurus mucrosquamatus) venom.

  Qiumin Lu, Alexei Navdaev, Jeannine M Clemetson, Kenneth J Clemetson
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  ABSTRACT: Mucetin (Trimeresurus mucrosquamatus venom activator, TMVA) is a potent platelet activator purified from Chinese habu (Trimeresurus mucrosquamatus) venom. It belongs to the snake venom heterodimeric C-type lectin family and exists in several multimeric forms. We now show that binding to platelet glycoprotein (GP) Ib is involved in mucetin-induced platelet aggregation. Antibodies against GPIb as well as the GPIb-blocking C-type lectin echicetin inhibited mucetin-induced platelet aggregation. Binding of GPIb was confirmed by affinity chromatography and Western blotting. Antibodies against GPVI inhibited convulxin- but not mucetin-induced aggregation. Signalling by mucetin involved rapid tyrosine phosphorylation of a number of proteins including Syk, Src, LAT and PLC gamma 2. Mucetin-induced phosphorylation of the Fc gamma chain of platelet was greatly promoted by inhibition of alpha(IIb)beta(3) by the peptidomimetic EMD 132338, suggesting that phosphatases downstream of alpha(IIb)beta(3) activation are involved in dephosphorylation of Fc gamma. Unlike other multimeric snake C-type lectins that act via GPIb and only agglutinate platelets, mucetin activates alpha(IIb)beta(3). Inhibition of alpha(IIb)beta(3) strongly reduced the aggregation response to mucetin, indicating that activation of alpha(IIb)beta(3) and binding of fibrinogen are involved in mucetin-induced platelet aggregation. Apyrase and aspirin also inhibit platelet aggregation induced by mucetin, suggesting that ADP and thromboxane A2 are involved in autocrine feedback. Sequence and structural comparison with closely related members of this protein family point to features that may be responsible for the functional differences.
  Thrombosis and Haemostasis 07/2004; 91(6):1168-76. · 5.04 Impact Factor
• Article: Purification and cloning of cysteine-rich proteins from Trimeresurus jerdonii and Naja atra venoms.

  Yang Jin, Qiumin Lu, Xingding Zhou, Shaowen Zhu, Rui Li, Wanyu Wang, Yuliang Xiong
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  ABSTRACT: Three 26 kDa proteins, named as TJ-CRVP, NA-CRVP1 and NA-CRVP2, were isolated from the venoms of Trimeresurus jerdonii and Naja atra, respectively. The N-terminal sequences of TJ-CRVP and NA-CRVPs were determined. These components were devoid of the enzymatic activities tested, such as phospholipase A(2), arginine esterase, proteolysis, L-amino acid oxidase, 5'nucleotidase, acetylcholinesterase. Furthermore, these three components did not have the following biological activities: coagulant and anticoagulant activities, lethal activity, myotoxicity, hemorrhagic activity, platelet aggregation and platelet aggregation-inhibiting activities. These proteins are named as cysteine-rich venom protein (CRVP) because their sequences showed high level of similarity with mammalian cysteine-rich secretory protein (CRISP) family. Recently, some CRISP-like proteins were also isolated from several different snake venoms, including Agkistrodon blomhoffi, Trimeresurus flavoviridis, Lanticauda semifascita and king cobra. We presumed that CRVP might be a common component in snake venoms. Of particular interest, phylogenetic analysis and sequence alignment showed that NA-CRVP1 and ophanin, both from elapid snakes, share higher similarity with CRVPs from Viperidae snakes.
  Toxicon 11/2003; 42(5):539-47. · 2.51 Impact Factor