The Experts below are selected from a list of 17208 Experts worldwide ranked by ideXlab platform
Francis S Markland - One of the best experts on this subject based on the ideXlab platform.
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Snake Venom fibrin ogen olytic enzymes
Toxicon, 2005Co-Authors: Steve Swenson, Francis S MarklandAbstract:Abstract Snake Venoms contain a number of serine and metalloproteinases and included among these are the fibrin(ogen)olytic proteinases. Some years ago it was postulated that the fibrin(ogen)olytic enzymes may be clinically useful. Over the past 150 years a substantial body of literature has been generated on the identification and characterization of fibrin(ogen)olytic enzymes from a broad spectrum of Snake species. In this review we describe the two different classes of fibrin(ogen)olytic enzymes isolated from Snake Venom and we summarize a number of studies aimed at characterizing the purified enzymes and/or their derivatives. Two distinct classes of Venom fibrin(ogen)olytic enzymes have been previously identified, the metalloproteinases and serine proteinases. These two classes of proteinases differ in their mechanism of action and they target different amino acid sequences in fibrin(ogen), but each perform the same role in nature. When a Snake enVenomates its prey it needs a mechanism to facilitate the spread of the toxic components throughout the circulation. Fibrin(ogen)olytic enzymes break down fibrin rich clots and help to prevent further clot formation by their action on fibrinogen. This characteristic feature has led to development of fibrin(ogen)olytic Snake Venom enzymes as potential clinical agents to treat occlusive thrombi. Fibrolase, a fibrinolytic metalloproteinase isolated from Agkistrodon contortrix contortrix Venom and the serine β-fibrinogenolytic proteinase from Vipera lebetina have been chosen as representative enzymes from the two classes, and their biochemical and physiochemical properties will be described in detail. Finally, the characterization and development of alfimeprase, a recombinant fibrinolytic enzyme derived from fibrolase, as a clinical agent is described citing the progression from the laboratory bench to its current status as having successfully completed Phase II clinical trials.
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Snake Venom fibrin ogen olytic enzymes
Toxicon, 2005Co-Authors: Steve Swenson, Francis S MarklandAbstract:Snake Venoms contain a number of serine and metalloproteinases and included among these are the fibrin(ogen)olytic proteinases. Some years ago it was postulated that the fibrin(ogen)olytic enzymes may be clinically useful. Over the past 150 years a substantial body of literature has been generated on the identification and characterization of fibrin(ogen)olytic enzymes from a broad spectrum of Snake species. In this review we describe the two different classes of fibrin(ogen)olytic enzymes isolated from Snake Venom and we summarize a number of studies aimed at characterizing the purified enzymes and/or their derivatives. Two distinct classes of Venom fibrin(ogen)olytic enzymes have been previously identified, the metalloproteinases and serine proteinases. These two classes of proteinases differ in their mechanism of action and they target different amino acid sequences in fibrin(ogen), but each perform the same role in nature. When a Snake enVenomates its prey it needs a mechanism to facilitate the spread of the toxic components throughout the circulation. Fibrin(ogen)olytic enzymes break down fibrin rich clots and help to prevent further clot formation by their action on fibrinogen. This characteristic feature has led to development of fibrin(ogen)olytic Snake Venom enzymes as potential clinical agents to treat occlusive thrombi. Fibrolase, a fibrinolytic metalloproteinase isolated from Agkistrodon contortrix contortrix Venom and the serine beta-fibrinogenolytic proteinase from Vipera lebetina have been chosen as representative enzymes from the two classes, and their biochemical and physiochemical properties will be described in detail. Finally, the characterization and development of alfimeprase, a recombinant fibrinolytic enzyme derived from fibrolase, as a clinical agent is described citing the progression from the laboratory bench to its current status as having successfully completed Phase II clinical trials.
Takashi Morita - One of the best experts on this subject based on the ideXlab platform.
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structure and function of Snake Venom cysteine rich secretory proteins
Toxicon, 2004Co-Authors: Yasuo Yamazaki, Takashi MoritaAbstract:Cysteine-rich secretory proteins (CRISPs) are primarily found in the epididymis of mammals and are expressed in diverse organisms. However, the functions of most CRISPs remain unknown. Recent studies reveal that CRISPs are widely distributed in Snake Venoms and that they inhibit smooth muscle contraction and cyclic nucleotide-gated ion channels. In this review, we discuss recent findings on several Snake Venom-derived CRISPs.
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Snake Venom vascular endothelial growth factors vegfs exhibit potent activity through their specific recognition of kdr vegf receptor 2
Journal of Biological Chemistry, 2003Co-Authors: Yasuo Yamazaki, Koji Takani, Hideko Atoda, Takashi MoritaAbstract:Abstract Vascular endothelial growth factor (VEGF165) exhibits multiple effects via the activation of two distinct endothelial receptor tyrosine kinases: Flt-1 (fms-like tyrosine kinase-1) and KDR (kinase insert domain-containing receptor). KDR shows strong ligand-dependent tyrosine phosphorylation in comparison with Flt-1 and mainly mediates the mitogenic, angiogenic, and permeability-enhancing effects of VEGF165. Here we show the isolation of two VEGFs from viper Venoms and the characterization of their unique biological properties. Snake Venom VEGFs strongly stimulated proliferation of vascular endothelial cells in vitro. Interestingly, the maximum activities were almost twice that of VEGF165. They also induced strong hypotension on rat arterial blood pressure compared with VEGF165 in vivo. A receptor binding assay revealed that Snake Venom VEGFs bound to KDR-IgG with high affinity (Kd = ∼0.1 nm) as well as to VEGF165 but did not interact with Flt-1, Flt-4, or neuropilin-1 at all. Our data clearly indicate that Snake Venom VEGFs act through the specific activation of KDR and show potent effects. Snake Venom VEGFs are a highly specific ligand to KDR and form a new group of the VEGF family.
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wide distribution of cysteine rich secretory proteins in Snake Venoms isolation and cloning of novel Snake Venom cysteine rich secretory proteins
Archives of Biochemistry and Biophysics, 2003Co-Authors: Yasuo Yamazaki, Fumiko Hyodo, Takashi MoritaAbstract:Cysteine-rich secretory proteins (CRISPs) are found in epididymis and granules of mammals, and they are thought to function in sperm maturation and in the immune system. Recently, we isolated and obtained clones for novel Snake Venom proteins that are classified as CRISP family proteins. To elucidate the distribution of Snake Venom CRISP family proteins, we evaluated a wide range of Venoms for immuno-cross-reactivity. Then we isolated, characterized, and cloned genes for three novel CRISP family proteins (piscivorin, ophanin, and catrin) from the Venom of eastern cottonmouth (Agkistrodon piscivorus piscivorus), king cobra (Ophiophagus hannah), and western diamondback rattleSnake (Crotalus atrox). Our results show the wide distribution of Snake Venom CRISP family proteins among Viperidae and Elapidae from different continents, indicating that CRISP family proteins compose a new group of Snake Venom proteins.
Steve Swenson - One of the best experts on this subject based on the ideXlab platform.
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Snake Venom fibrin ogen olytic enzymes
Toxicon, 2005Co-Authors: Steve Swenson, Francis S MarklandAbstract:Abstract Snake Venoms contain a number of serine and metalloproteinases and included among these are the fibrin(ogen)olytic proteinases. Some years ago it was postulated that the fibrin(ogen)olytic enzymes may be clinically useful. Over the past 150 years a substantial body of literature has been generated on the identification and characterization of fibrin(ogen)olytic enzymes from a broad spectrum of Snake species. In this review we describe the two different classes of fibrin(ogen)olytic enzymes isolated from Snake Venom and we summarize a number of studies aimed at characterizing the purified enzymes and/or their derivatives. Two distinct classes of Venom fibrin(ogen)olytic enzymes have been previously identified, the metalloproteinases and serine proteinases. These two classes of proteinases differ in their mechanism of action and they target different amino acid sequences in fibrin(ogen), but each perform the same role in nature. When a Snake enVenomates its prey it needs a mechanism to facilitate the spread of the toxic components throughout the circulation. Fibrin(ogen)olytic enzymes break down fibrin rich clots and help to prevent further clot formation by their action on fibrinogen. This characteristic feature has led to development of fibrin(ogen)olytic Snake Venom enzymes as potential clinical agents to treat occlusive thrombi. Fibrolase, a fibrinolytic metalloproteinase isolated from Agkistrodon contortrix contortrix Venom and the serine β-fibrinogenolytic proteinase from Vipera lebetina have been chosen as representative enzymes from the two classes, and their biochemical and physiochemical properties will be described in detail. Finally, the characterization and development of alfimeprase, a recombinant fibrinolytic enzyme derived from fibrolase, as a clinical agent is described citing the progression from the laboratory bench to its current status as having successfully completed Phase II clinical trials.
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Snake Venom fibrin ogen olytic enzymes
Toxicon, 2005Co-Authors: Steve Swenson, Francis S MarklandAbstract:Snake Venoms contain a number of serine and metalloproteinases and included among these are the fibrin(ogen)olytic proteinases. Some years ago it was postulated that the fibrin(ogen)olytic enzymes may be clinically useful. Over the past 150 years a substantial body of literature has been generated on the identification and characterization of fibrin(ogen)olytic enzymes from a broad spectrum of Snake species. In this review we describe the two different classes of fibrin(ogen)olytic enzymes isolated from Snake Venom and we summarize a number of studies aimed at characterizing the purified enzymes and/or their derivatives. Two distinct classes of Venom fibrin(ogen)olytic enzymes have been previously identified, the metalloproteinases and serine proteinases. These two classes of proteinases differ in their mechanism of action and they target different amino acid sequences in fibrin(ogen), but each perform the same role in nature. When a Snake enVenomates its prey it needs a mechanism to facilitate the spread of the toxic components throughout the circulation. Fibrin(ogen)olytic enzymes break down fibrin rich clots and help to prevent further clot formation by their action on fibrinogen. This characteristic feature has led to development of fibrin(ogen)olytic Snake Venom enzymes as potential clinical agents to treat occlusive thrombi. Fibrolase, a fibrinolytic metalloproteinase isolated from Agkistrodon contortrix contortrix Venom and the serine beta-fibrinogenolytic proteinase from Vipera lebetina have been chosen as representative enzymes from the two classes, and their biochemical and physiochemical properties will be described in detail. Finally, the characterization and development of alfimeprase, a recombinant fibrinolytic enzyme derived from fibrolase, as a clinical agent is described citing the progression from the laboratory bench to its current status as having successfully completed Phase II clinical trials.
Yasuo Yamazaki - One of the best experts on this subject based on the ideXlab platform.
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structure and function of Snake Venom cysteine rich secretory proteins
Toxicon, 2004Co-Authors: Yasuo Yamazaki, Takashi MoritaAbstract:Cysteine-rich secretory proteins (CRISPs) are primarily found in the epididymis of mammals and are expressed in diverse organisms. However, the functions of most CRISPs remain unknown. Recent studies reveal that CRISPs are widely distributed in Snake Venoms and that they inhibit smooth muscle contraction and cyclic nucleotide-gated ion channels. In this review, we discuss recent findings on several Snake Venom-derived CRISPs.
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Snake Venom vascular endothelial growth factors vegfs exhibit potent activity through their specific recognition of kdr vegf receptor 2
Journal of Biological Chemistry, 2003Co-Authors: Yasuo Yamazaki, Koji Takani, Hideko Atoda, Takashi MoritaAbstract:Abstract Vascular endothelial growth factor (VEGF165) exhibits multiple effects via the activation of two distinct endothelial receptor tyrosine kinases: Flt-1 (fms-like tyrosine kinase-1) and KDR (kinase insert domain-containing receptor). KDR shows strong ligand-dependent tyrosine phosphorylation in comparison with Flt-1 and mainly mediates the mitogenic, angiogenic, and permeability-enhancing effects of VEGF165. Here we show the isolation of two VEGFs from viper Venoms and the characterization of their unique biological properties. Snake Venom VEGFs strongly stimulated proliferation of vascular endothelial cells in vitro. Interestingly, the maximum activities were almost twice that of VEGF165. They also induced strong hypotension on rat arterial blood pressure compared with VEGF165 in vivo. A receptor binding assay revealed that Snake Venom VEGFs bound to KDR-IgG with high affinity (Kd = ∼0.1 nm) as well as to VEGF165 but did not interact with Flt-1, Flt-4, or neuropilin-1 at all. Our data clearly indicate that Snake Venom VEGFs act through the specific activation of KDR and show potent effects. Snake Venom VEGFs are a highly specific ligand to KDR and form a new group of the VEGF family.
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wide distribution of cysteine rich secretory proteins in Snake Venoms isolation and cloning of novel Snake Venom cysteine rich secretory proteins
Archives of Biochemistry and Biophysics, 2003Co-Authors: Yasuo Yamazaki, Fumiko Hyodo, Takashi MoritaAbstract:Cysteine-rich secretory proteins (CRISPs) are found in epididymis and granules of mammals, and they are thought to function in sperm maturation and in the immune system. Recently, we isolated and obtained clones for novel Snake Venom proteins that are classified as CRISP family proteins. To elucidate the distribution of Snake Venom CRISP family proteins, we evaluated a wide range of Venoms for immuno-cross-reactivity. Then we isolated, characterized, and cloned genes for three novel CRISP family proteins (piscivorin, ophanin, and catrin) from the Venom of eastern cottonmouth (Agkistrodon piscivorus piscivorus), king cobra (Ophiophagus hannah), and western diamondback rattleSnake (Crotalus atrox). Our results show the wide distribution of Snake Venom CRISP family proteins among Viperidae and Elapidae from different continents, indicating that CRISP family proteins compose a new group of Snake Venom proteins.
Solange M T Serrano - One of the best experts on this subject based on the ideXlab platform.
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the long road of research on Snake Venom serine proteinases
Toxicon, 2013Co-Authors: Solange M T SerranoAbstract:It has long been recognized that Snake Venom serine proteinases (SVSPs) affect various physiological functions including blood coagulation, fibrinolysis, blood pressure and platelet aggregation. Therefore, SVSPs have been used as refined tools to study molecular mechanisms involved in the activation of key factors that control hemostasis and as therapeutic agents in various thrombotic and hemostatic conditions. The aim of this review is to highlight the state of our knowledge on the advances made in SVSP research since the 18th century. It includes the personal accounts of some distinguished scientists that addressed specific problems and contributed to advance the field.
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timeline of key events in Snake Venom metalloproteinase research
Journal of Proteomics, 2009Co-Authors: Jay W Fox, Solange M T SerranoAbstract:It is reasonable to state that Snake Venom toxinology has been actively pursued for at least the past 400 to 500 years. Early on it was appreciated that the Venoms of the Viperidae produced profound local effects, notably hemorrhage. For the past 100 years, with the advent of modern chemistry and biochemistry significant progress has been gained regarding the function, structure and role of the Snake Venom metalloproteinases (SVMPs) in viperid Venom pathogenesis. In this review we provide a concise, chronological presentation of the key significant studies that have led to our current understanding of these intriguing toxins.
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insights into and speculations about Snake Venom metalloproteinase svmp synthesis folding and disulfide bond formation and their contribution to Venom complexity
FEBS Journal, 2008Co-Authors: Jay W Fox, Solange M T SerranoAbstract:As more data are generated from proteome and transcriptome analyses of Snake Venoms, we are gaining an appreciation of the complexity of the Venoms and, to some degree, the various sources of such complexity. However, our knowledge is still far from complete. The translation of genetic information from the Snake genome to the transcriptome and ultimately the proteome is only beginning to be appreciated, and will require significantly more investigation of the Snake Venom genomic structure prior to a complete understanding of the genesis of Venom composition. Venom complexity, however, is derived not only from the Venom genomic structure but also from transcriptome generation and translation and, perhaps most importantly, post-translation modification of the nascent Venom proteome. In this review, we examine the Snake Venom metalloproteinases, some of the predominant components in viperid Venoms, with regard to possible synthesis and post-translational mechanisms that contribute to Venom complexity. The aim of this review is to highlight the state of our knowledge on Snake Venom metalloproteinase post-translational processing and to suggest testable hypotheses regarding the cellular mechanisms associated with Snake Venom metalloproteinase complexity in Venoms.
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exploring Snake Venom proteomes multifaceted analyses for complex toxin mixtures
Proteomics, 2008Co-Authors: Jay W Fox, Solange M T SerranoAbstract:Snake Venom proteomes are complex mixtures of a large number of distinct proteins. In a sense, the field of Snake Venom proteomics has been under investigation since the very earliest biochemical studies on Venoms where peptides and proteins were isolated and structurally and biologically characterized. With the recent developments in mass spectrometry for the identification of proteins, coupled with Venom gland transcriptomes, has the field of Snake Venom proteomics began to flourish. These developments have led to exciting insights into the protein composition of Venoms and subsequently their pathological activities. In this review, we will discuss the state of art of Snake Venom proteomics. Although we have not reached the ultimate goal of characterizing and quantifying all unique proteins in a Venom proteome, current technologies have opened many opportunities for high-throughput proteomic studies that have gone beyond simple protein identification to analyzing various functional aspects, such as post-translational modifications, proteolytic processing and toxin-target interactions. In this review, we will discuss the technological approaches used in the study of Venom proteomics highlighting the advances made and future directions.