Inhibition of mammalian and snake venom metalloproteinases by the recombinant pro-domain of jararhagin and its relevant peptide fragments

• Grant number: 14/26058-8
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2015 - March 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Ana Maria Moura da Silva
• Grantee: Ana Maria Moura da Silva
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Geraldo Santana Magalhães ; Patricia Bianca Clissa

Abstract

Zinc-dependent metalloproteinases are enzymes essential for homeostasis particularly MMPs (Matrix Metalloproteinases) and ADAMs (A Disintegrin And Metalloproteinase) that are involved in a wide variety of biological processes ranging from physiological cell proliferation and differentiation to pathological states associated with tumor metastasis, inflammation, tissue degeneration, and cell death. Snake Venom Metalloproteinases (SVMPs) are abundant in venoms of viper snakes and responsible for most local and systemic symptoms of human envenomings. Thus, several studies have been carried out in order to achieve natural or synthetic inhibitors able to neutralize the pathological effects of these enzymes. MMPs, ADAMs and SVMPs are synthesized as zymogens and the enzyme activation is regulated by hydrolysis of its pro-domain. In recent studies, our group has shown that SVMP processing occurs in the secretory vesicles and is completed in the lumen of the venom gland where the pro-domain undergoes fast hydrolysis to peptides detected in the venom. In this project, we aim to evaluate the inhibition of MMPs, ADAMs and SVMPs catalytic activity by the recombinant pro-domain of jararhagin and the peptidic fragments detected on venom peptidome. Moreover, the potential applicability of the peptides will be accessed by the inhibition of venom-induced effects and the release of inflammatory mediators by snake venom components or proinflammatory agents that may lead to new approaches for designing inhibitors with therapeutic purposes. (AU)

Scientific publications

(9)

(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)

ALMEIDA, MICHELLE TEIXEIRA DE; FREITAS-DE-SOUSA, LUCIANA APARECIDA; COLOMBINI, MONICA; GIMENES, SARAH N. C.; KITANO, EDUARDO S.; FAQUIM-MAURO, ELIANA L.; SERRANO, SOLANGE M. T.; MOURA-DA-SILVA, ANA MARIA. Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components. TOXINS, v. 12, n. 2, FEB 2020. (13/07467-1, 16/50127-5, 14/26058-8)

FREITAS-DE-SOUSA, LUCIANA APARECIDA; COLOMBINI, MONICA; LOPES-FERREIRA, MONICA; SERRANO, SOLANGE M. T.; MOURA-DA-SILVA, ANA MARIA. Insights into the Mechanisms Involved in Strong Hemorrhage and Dermonecrosis Induced by Atroxlysin-Ia, a PI-Class Snake Venom Metalloproteinase. TOXINS, v. 9, n. 8, AUG 2017. (13/07467-1, 16/50127-5, 14/26058-8)

LIMA-DOS-SANTOS, I.; DELLA-CASA, M. S.; PORTES-JUNIOR, J. A.; CALABRIA, P. A. L.; MAGALHAES, G. S.; MOURA-DA-SILVA, A. M.. Characterization of Neuwiedin, a new disintegrin from Bothrops neuwiedi venom gland with distinct cysteine pattern. Toxicon, v. 104, p. 57-64, SEP 15 2015. (12/16277-9, 10/13559-8, 14/26058-8)

MOURA-DA-SILVA, ANA M.; ALMEIDA, MICHELLE T.; PORTES-JUNIOR, JOSE A.; NICOLAU, CAROLINA A.; GOMES-NETO, FRANCISCO; VALENTE, RICHARD H.. Processing of Snake Venom Metalloproteinases: Generation of Toxin Diversity and Enzyme Inactivation. TOXINS, v. 8, n. 6, JUN 2016. (14/26058-8)

SOUSA, LEIJIANE F.; PORTES-JUNIOR, JOSE A.; NICOLAU, CAROLINA A.; BERNARDONI, JULIANA L.; NISHIYAMA-, JR., MILTON Y.; AMAZONAS, DIANA R.; FREITAS-DE-SOUSA, LUCIANA A.; MOURAO, ROSA H. V.; CHALKIDIS, HIPOCRATES M.; VALENTE, RICHARD H.; et al. Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon. JOURNAL OF PROTEOMICS, v. 159, p. 32-46, APR 21 2017. (14/13124-2, 12/16277-9, 14/26058-8, 14/13592-6)

VALENTE, RICHARD HEMMI; LUNA, MILENE SCHMIDT; DE OLIVEIRA, URSULA CASTRO; NISHIYAMA-JUNIOR, MILTON YUTAKA; JUNQUEIRA-DE-AZEVEDO, INACIO DE LOIOLA; PORTES-JUNIOR, JOSE ANTONIO; CLISSA, PATRICIA BIANCA; VIANA, LUCIANA GODOY; SANCHES, LEONARDO; MOURA-DA-SILVA, ANA MARIA; et al. Bothrops jararaca accessory venom gland is an ancillary source of toxins to the snake. JOURNAL OF PROTEOMICS, v. 177, p. 137-147, APR 15 2018. (13/07467-1, 14/26058-8, 16/50127-5)

KNITTEL, PALOMA S.; LONG, PAUL F.; BRAMMALL, LUCAS; MARQUES, ANTONIO C.; ALMEIDA, MICHELLE T.; PADILLA, GABRIEL; MOURA-DA-SILVA, ANA M.. Characterising the enzymatic profile of crude tentacle extracts from the South Atlantic jellyfish Olindias sambaquiensis (Cnidaria: Hydrozoa). Toxicon, v. 119, p. 1-7, SEP 1 2016. (11/50242-5, 14/26058-8, 13/25593-4)

AMAZONAS, DIANA R.; PORTES-JUNIOR, JOSE A.; NISHIYAMA-JR, MILTON Y.; NICOLAU, CAROLINA A.; CHALKIDIS, HIPOCRATES M.; MOURAO, V, ROSA H.; GRAZZIOTIN, FELIPE G.; ROKYTA, DARIN R.; LISLE GIBBS, H.; VALENTE, RICHARD H.; et al. Molecular mechanisms underlying intraspecific variation in snake venom. JOURNAL OF PROTEOMICS, v. 181, p. 60-72, JUN 15 2018. (12/16277-9, 16/50127-5, 14/26058-8)

FREITAS-DE-SOUSA, L. A.; AMAZONAS, D. R.; SOUSA, L. F.; SANT'ANNA, S. S.; NISHIYAMA, JR., M. Y.; SERRANO, S. M. T.; JUNQUEIRA-DE-AZEVEDO, I. L. M.; CHALKIDIS, H. M.; MOURA-DA-SILVA, A. M.; MOURAO, R. H. V.. Comparison of venoms from wild and long-term captive Bothrops atrox snakes and characterization of Batroxrhagin, the predominant class PIII metalloproteinase from the venom of this species. Biochimie, v. 118, p. 60-70, NOV 2015. (13/07467-1, 12/16277-9, 14/26058-8)