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Study of the degradome of HF3, a PIII-class snake venom metalloproteinase from Bothrops jararaca venom, on cultured fibroblasts

Grant number: 11/08514-8
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): July 01, 2011
Effective date (End): September 30, 2013
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Solange Maria de Toledo Serrano
Grantee:André Zelanis Palitot Pereira
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:98/14307-9 - Center for Applied Toxinology, AP.CEPID
Associated scholarship(s):11/23403-8 - Study of the degradome of HF3, a PIII-class snake venom metalloproteinase from Bothrops jararaca venom, on cultured fibroblasts, BE.EP.PD


Proteinases are the major components of viperid venom proteomes. In this context, snake venom metalloproteinases (SVMPs) are among the most abundant enzymes found in venoms and are responsible for several of the pathological effects of envenomation. The structural similarity of SVMPs with ADAMs (A Disintegrin and Metalloproteinase) and ADAMTSs (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) has guided a number of functional assays currently employed in toxinology studies. The study of SVMPs activities in complex biological systems with the use of omics technologies has allowed the evaluation of several aspects of the pathology of the ophidian envenomation, as well as the signaling pathways triggered by SVMPs. Using complementary methodologies in proteomics and mass spectrometry the main goals of this project are to identify the alterations in the proteome of cultured fibroblasts subjected to the activity of HF3, a highly hemorrhagic P-III class SVMP isolated from Bothrops jararaca venom, as well as to evaluate in a high throughput fashion the substrate repertoire (degradome) of HF3 in cultured fibroblasts. The importance of this work is related to the use of a holistic approach for a better understanding of direct and indirect mechanisms of activity of HF3 upon cells. Moreover, the new findings will serve as a basis for the study of other metalloproteinases found in venoms or in the extracellular matrix of other vertebrates. (AU)

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Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BERTHOLIM, LUCIANA; CHAVES, ALISON F. A.; OLIVEIRA, ANA K.; MENEZES, MILENE C.; ASEGA, AMANDA F.; TASHIMA, ALEXANDRE K.; ZELANIS, ANDRE; SERRANO, SOLANGE M. T.. Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins. TOXINS, v. 13, n. 11, . (11/08514-8, 20/12317-2, 11/16623-1, 13/07467-1)
LIBERATO, TARCISIO; PAOLO TRONCONE, LANFRANCO RANIERI; YAMASHIRO, EDSON T.; SERRANO, SOLANGE M. T.; ZELANIS, ANDRE. High-resolution proteomic profiling of spider venom: expanding the toxin diversity of Phoneutria nigriventer venom. Amino Acids, v. 48, n. 3, p. 901-906, . (13/07467-1, 11/08514-8)
ZELANIS, ANDRE; HUESGEN, PITTER F.; OLIVEIRA, ANA KARINA; TASHIMA, ALEXANDRE K.; SERRANO, SOLANGE M. T.; OVERALL, CHRISTOPHER M.. Snake venom serine proteinases specificity mapping by proteomic identification of cleavage sites. JOURNAL OF PROTEOMICS, v. 113, p. 260-267, . (13/07467-1, 10/17328-0, 11/23403-8, 11/08514-8)
YAMASHIRO, EDSON T.; OLIVEIRA, ANA K.; KITANO, EDUARDO S.; MENEZES, MILENE C.; JUNQUEIRA-DE-AZEVEDO, INACIO L.; LEME, ADRIANA F. PAES; SERRANO, SOLANGE M. T.. Proteoforms of the platelet-aggregating enzyme PA-BJ, a serine proteinase from Bothrops jararaca venom. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1844, n. 12, p. 2068-2076, . (13/07467-1, 11/11308-0, 11/08514-8, 98/14307-9)
KITANO, EDUARDO S.; GARCIA, THALITA C.; MENEZES, MILENE C.; TASHIMA, ALEXANDRE K.; ZELANIS, ANDRE; SERRANO, SOLANGE M. T.. Cotiarinase is a novel prothrombin activator from the venom of Bothrops cotiara. Biochimie, v. 95, n. 8, p. 1655-1659, . (11/11308-0, 11/08514-8, 98/14307-9)
ASEGA, AMANDA F. .; MENEZES, MILENE C.; TREVISAN-SILVA, DILZA; CAJADO-CARVALHO, DANIELA; BERTHOLIM, LUCIANA; OLIVEIRA, ANA K.; ZELANIS, ANDRE; SERRANO, SOLANGE M. T.. Cleavage of proteoglycans, plasma proteins and the platelet-derived growth factor receptor in the hemorrhagic process induced by snake venom metalloproteinases. SCIENTIFIC REPORTS, v. 10, n. 1, . (17/00715-0, 10/00206-0, 17/19252-0, 10/17328-0, 11/08514-8, 13/07467-1)
ZELANIS, ANDRE; OLIVEIRA, ANA K.; PRUDOVA, ANNA; HUESGEN, PITTER F.; TASHIMA, ALEXANDRE K.; KIZHAKKEDATHU, JAYACHANDRAN; OVERALL, CHRISTOPHER M.; SERRANO, SOLANGE M. T.. Deep Profiling of the Cleavage Specificity and Human Substrates of Snake Venom Metalloprotease HF3 by Proteomic Identification of Cleavage Site Specificity (PICS) Using Proteome Derived Peptide Libraries and Terminal Amine Isotopic Labeling of Substrates (TAILS) N-Terminomics. JOURNAL OF PROTEOME RESEARCH, v. 18, n. 9, p. 3419-3428, . (13/07467-1, 11/23403-8, 11/08514-8, 10/17328-0)

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