Phospholipase A2 inhibitors (PLIs) present in venomous and non-venomous snake plasmas and evaluation of the neutralizing activity of these inhibitors on the phospholipase A2 (PLA2) activities of snake venoms

• Grant number: 18/25786-0
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2019
• End date: April 30, 2022
• Field of knowledge: Biological Sciences - Physiology - Compared Physiology
• Principal Investigator: Anita Mitico Tanaka-Azevedo
• Grantee: Anita Mitico Tanaka-Azevedo
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Alexandre Keiji Tashima ; Aparecida Sadae Tanaka ; Benedito Carlos Prezoto ; Karen de Morais Zani ; Kathleen Fernandes Grego

Abstract

There is a great diversity of venomous and non-venomous snakes in Brazil and in the world. The biological and behavioral differences of these two groups have been increasingly studied. Venomous snakes are responsible for 5 million human accidents per year, a fact that encourages knowledge about all aspects of envenomation. Nowadays, it is known that 90% of the venom of these snakes is composed of about 15 families of proteins that trigger the systemic and local effects of envenomation. The use of serum therapy in this treatment has been efficient in minimizing the systemic effects, however, the difficult access to adequate serum and the rapid action of some families of proteins (mainly metalloproteases and phospholipases A2) developed by local symptoms are not totally neutralized, leading to around 400 thousand amputations per year. So, the study of proteins present in the blood of animals has been one of the alternatives found for the development of new drugs, which can contribute in the neutralization of these effects. Inhibitors of phospholipases A2 (PLI) have been one of the major targets of these studies, for the ability to neutralize many effects of different classes of PLA2, including human ones. The presence of these PLIs in different animals (venomous snakes, non-venomous snakes and mammals) has also stimulated the interest by their biological role as well as their mechanism of action.Thus, in recent years, our group has been studying venom and plasma proteins from snakes. We have recently isolated a serum ³-type PLI from the venomous snake Bothrops jararaca (B. jararaca) plasma and, we have also elucidated some characteristics of its structure and inhibitory action of the enzymatic, edematogenic and myionecrotic activity of PLA2. Thus, the isolation of a PLI of Boa constrictor, a non-venomous snake, the comparison of this inhibitor with B. jararaca plasma PLI, as well as the elucidation of the mechanism of action of both inhibitors in the envenomation and inflammatory processes, will contribute for the development of new alternatives that complement the treatment of ophidian accidents, besides contributing to the elucidation of the physiological role of these proteins in these animals. (AU)

Scientific publications

(18)

(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)

RODRIGUES, CAROLINE FABRI BITTENCOURT; ZDENEK, CHRISTINA N.; SERINO-SILVA, CAROLINE; DE MORAIS-ZANI, KAREN; GREGO, KATHLEEN FERNANDES; BENARD-VALLE, MELISA; NERI-CASTRO, EDGAR; ALAGON, ALEJANDRO; TANAKA-AZEVEDO, ANITA MITICO; FRY, BRYAN GRIEG. Boa gamma PLI from Boa constrictor Blood is a Broad-Spectrum Inhibitor of Venom PLA(2) Pathophysiological Actions. Journal of Chemical Ecology, JUN 2021. (18/25786-0)

LEANDRO NORBERTO DA SILVA-JÚNIOR; LARA DE SOUZA ABREU; CAROLINE FABRI BITTENCOURT RODRIGUES; NATHÁLIA DA COSTA GALIZIO; WESLEI DA SILVA AGUIAR; CAROLINE SERINO-SILVA; VALDOMIRO SOUZA DOS SANTOS; ISABELLA ALVES COSTA; LUIS VICENTE FRANCO OLIVEIRA; SÁVIO STEFANINI SANTANNA; et al. Geographic variation of individual venom profile of Crotalus durissus snakes. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, 2020-08-26. (18/25786-0, 14/11108-0, 16/09976-9, 18/14724-4, 17/16908-2, 17/01890-0)

SIMIZO, ADRIANA; KITANO, EDUARDO S.; SANT'ANNA, SAVIO S.; GREGO, KATHLEEN FERNANDES; TANAKA-AZEVEDO, ANITA MITICO; TASHIMA, ALEXANDRE K.. Comparative gender peptidomics of Bothrops atrox venoms: are there differences between them?. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, p. 17-pg., 2020-10-07. (19/03502-3, 17/20106-9, 18/25786-0)

AGUIAR, WESLEI DA SILVA; GALIZIO, NATHALIA DA COSTA; GREGO, KATHLEEN FERNANDES; MACHADO DA SILVEIRA, GIOVANNI PEREZ; DE MORAIS-ZANI, KAREN; TANAKA-AZEVEDO, ANITA MITICO. Bothrops jararacussu ontogenetic venom variability: from birth to adulthood. BIOPHYSICAL REVIEWS, v. 13, n. 6, p. 1-pg., 2021-12-01. (18/20651-0, 17/16908-2, 18/25786-0)

SERINO-SILVA, CAROLINE; BITTENCOURT RODRIGUES, CAROLINE FABRI; MIYAMOTO, JACKSON GABRIEL; HATAKEYAMA, DANIELA MIKI; KAVAZOI, VICTOR KOITI; DA ROCHA, MARISA MARIA TEIXEIRA; TANAKA, APARECIDA SADAE; TASHIMA, ALEXANDRE KEIJI; DE MORAIS-ZANI, KAREN; GREGO, KATHLEEN FERNANDES; et al. Proteomics and life-history variability of Endogenous Phospholipases A2 Inhibitors (PLIs) in Bothrops jararaca plasma. PLoS One, v. 19, n. 2, p. 19-pg., 2024-02-06. (21/11707-4, 18/25786-0, 19/03779-5, 12/03657-8, 17/20106-9)

DA SILVA-JUNIOR, LEANDRO NORBERTO; ABREU, LARA DE SOUZA; BITTENCOURT RODRIGUES, CAROLINE FABRI; GALIZIO, NATHALIA DA COSTA; AGUIAR, WESLEI DA SILVA; SERINO-SILVA, CAROLINE; DOS SANTOS, VALDOMIRO SOUZA; COSTA, ISABELLA ALVES; FRANCO OLIVEIRA, LUIS VICENTE; SANT'ANNA, SAVIO STEFANINI; et al. Geographic variation of individual venom profile of Crotalus durissus snakes. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, p. 16-pg., 2020-08-26. (17/01890-0, 18/14724-4, 18/25786-0, 16/09976-9, 17/16908-2, 14/11108-0)

HATAKEYAMA, DANIELA MIKI; TASIMA, LIDIA JORGE; GALIZIO, NATHALIA DA COSTA; SERINO-SILVA, CAROLINE; FABRI BITTENCOURT RODRIGUES, CAROLINE; STUGINSKI, DANIEL RODRIGUES; SANT'ANNA, SAVIO STEFANINI; GREGO, KATHLEEN FERNANDES; TASHIMA, ALEXANDRE KEIJI; NISHIDUKA, ERIKA SAYURI; et al. From birth to adulthood: An analysis of the Brazilian lancehead (Bothrops moojeni) venom at different life stages. PLoS One, v. 16, n. 6, JUN 10 2021. (17/16908-2, 17/20106-9, 18/25786-0, 18/25899-0, 18/14724-4)

HATAKEYAMA, DANIELA MIKI; MACHADO DA SILVEIRA, GIOVANNI PEREZ; SANT'ANNA, SAVIO STEFANINI; GREGO, KATHLEEN FERNANDES; ZANI, KAREN DE MORAIS; TANAKA AZEVEDO, ANITA MITICO. Ontogenetic and sexual comparison of Bothrops erythromelas (jararaca-da-seca) snake venom. BIOPHYSICAL REVIEWS, v. 13, n. 6, p. 2-pg., 2021-12-01. (18/25786-0)

VENANCIO DE LIMA, EDUARDO OLIVEIRA; TASIMA, LIDIA JORGE; HATAKEYAMA, DANIELA MIKI; SERINO-SILVA, CAROLINE; BITTENCOURT RODRIGUES, CAROLINE FABRI; GALIZIO, NATHALIA DA COSTA; CHIARELLI, TASSIA; NISHIDUKA, ERIKA SAYURI; TEIXEIRA DA ROCHA, MARISA MARIA; SANT'ANNA, SAVIO STEFANINI; et al. Snake venom color and L-amino acid oxidase: An evidence of long-term captive Crotalus durissus terrificus venom plasticity. Toxicon, v. 193, p. 73-83, APR 15 2021. (18/25786-0, 14/11108-0, 17/01890-0, 16/09976-9, 17/20106-9, 17/21052-0, 17/16908-2, 18/14724-4)

BITTENCOURT RODRIGUES, CAROLINE FABRI; SERINO-SILVA, CAROLINE; DE MORAIS-ZANI, KAREN; KAVAZOI, VICTOR KOITI; NOGUEIRA CARVALHO, MARCELO PIRES; GREGO, KATHLEEN FERNANDES; CHIARELLI, TASSIA; TASHIMA, ALEXANDRE KEIJI; TOYAMA, MARCOS HIKARI; TANAKA-AZEVEDO, ANITA MITICO. Boa.PLI: Structural and functional characterization of the gamma phospholipase A2 plasma inhibitor from the non-venomous Brazilian snake Boa constrictor. PLoS One, v. 15, n. 2, FEB 27 2020. (17/20106-9, 17/16908-2, 18/25786-0)

ADRIANA SIMIZO; EDUARDO S. KITANO; SÁVIO S. SANTANNA; KATHLEEN FERNANDES GREGO; ANITA MITICO TANAKA-AZEVEDO; ALEXANDRE K. TASHIMA. Comparative gender peptidomics of Bothrops atrox venoms: are there differences between them?. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, 2020-10-07. (17/20106-9, 17/21052-0, 18/25786-0, 19/03502-3)

MACHADO BRAGA, JACQUELINE RAMOS; DE MORAIS-ZANI, KAREN; PEREIRA, DIEGO DOS SANTOS; SANT'ANNA, SAVIO STEFANINI; GALIZIO, NATHALIA DA COSTA; TANAKA-AZEVEDO, ANITA MITICO; GOMES VILARINHO, ARIEL RODRIGUES; RODRIGUES, JOSE LUCCA; TEIXEIRA DA ROCHA, MARISA MARIA. Sexual and ontogenetic variation of Bothrops leucurus venom. Toxicon, v. 184, p. 127-135, SEP 2020. (14/11108-0, 18/14724-4, 17/16908-2, 16/09976-9, 18/25786-0)

RODRIGUES, CAROLINE FABRI BITTENCOURT; ZDENEK, CHRISTINA N.; SERINO-SILVA, CAROLINE; DE MORAIS-ZANI, KAREN; GREGO, KATHLEEN FERNANDES; BENARD-VALLE, MELISA; NERI-CASTRO, EDGAR; ALAGON, ALEJANDRO; TANAKA-AZEVEDO, ANITA MITICO; FRY, BRYAN GRIEG. Boa gamma PLI from Boa constrictor Blood is a Broad-Spectrum Inhibitor of Venom PLA(2) Pathophysiological Actions. Journal of Chemical Ecology, v. 47, n. 10-11, p. 907-914, NOV 2021. (18/25786-0)

TASIMA, LIDIA J.; HATAKEYAMA, DANIELA M.; SERINO-SILVA, CAROLINE; RODRIGUES, CAROLINE F. B.; DE LIMA, V, EDUARDO O.; SANT'ANNA, SAVIO S.; GREGO, KATHLEEN F.; DE MORAIS-ZANI, KAREN; SANZ, LIBIA; CALVETE, JUAN J.; et al. Comparative proteomic profiling and functional characterization of venom pooled from captive Crotalus durissus terrificus specimens and the Brazilian crotalic reference venom. Toxicon, v. 185, p. 26-35, OCT 15 2020. (17/01890-0, 17/16908-2, 18/25899-0, 17/26533-6, 18/25786-0)

TASIMA, LIDIA JORGE; HATAKEYAMA, DANIELA MIKI; AGUIAR, WESLEI DA SILVA; DE LIMA, EDUARDO OLIVEIRA VENACIOIO DE; MIYAMOTO, JACKSON GABRIEL; TASHIMA, ALEXANDRE KEIJI; GREGO, KATHLEEN FERNANDES; DE MORAIS-ZANI, KAREN; TANAKA-AZEVEDO, ANITA MITICO. Analyzing the influence of age and sex in Bothrops pauloensis snake venom. Toxicon, v. 214, p. 13-pg., 2022-07-30. (20/07268-2, 18/25899-0, 18/25786-0)

AGUIAR, WESLEI DA SILVA; GALIZIO, NATHALIA DA COSTA; SANT'ANNA, SAVIO STEFANINI; SILVEIRA, GIOVANNI PEREZ M.; RODRIGUES, FABIOLA DE SOUZA; GREGO, KATHLEEN FERNANDES; DE MORAIS-ZANI, KAREN; TANAKA-AZEVEDO, ANITA MITICO. Ontogenetic study of Bothrops jararacussu venom composition reveals distinct profiles. Toxicon, v. 186, p. 67-77, OCT 30 2020. (17/16908-2, 18/25786-0, 18/14724-4, 18/20651-0)

HATAKEYAMA, DANIELA MIKI; TASIMA, LIDIA JORGE; BRAVO-TOBAR, CESAR ADOLFO; SERINO-SILVA, CAROLINE; TASHIMA, ALEXANDRE KEIJI; BITTENCOURT RODRIGUES, CAROLINE FABRI; AGUIAR, WESLEI DA SILVA; GALIZIO, NATHALIA DA COSTA; VENANCIO DE LIMA, EDUARDO OLIVEIRA; KAVAZOI, VICTOR KOITI; et al. Venom complexity of Bothrops atrox (common lancehead) siblings. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, OCT 12 2020. (17/16908-2, 18/25786-0, 17/01890-0, 17/20106-9)

AGUIAR, WESLEI DA SILVA; GALIZIO, NATHALIA DA COSTA; SERINO-SILVA, CAROLINE; SANT'ANNA, SAVIO STEFANINI; GREGO, KATHLEEN FERNANDES; TASHIMA, ALEXANDRE KEIJI; NISHIDUKA, ERIKA SAYURI; DE MORAIS-ZANI, KAREN; TANAKA-AZEVEDO, ANITA MITICO. Comparative compositional and functional analyses of Bothrops moojeni specimens reveal several individual variations. PLoS One, v. 14, n. 9, SEP 12 2019. (17/01890-0, 17/16908-2, 14/11108-0, 17/20106-9, 18/20651-0, 18/14724-4, 18/25786-0)