Isolation, molecular and functional characterization of a new toxin from Tityus serrulatus scorpion venom

• Grant number: 12/13590-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2012
• End date: September 30, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Eliane Candiani Arantes Braga
• Grantee: Felipe Augusto Cerni
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 13/21342-7 - Electrophysiological characterization of Ts19 fragment II, a new toxin purified from Tityus serrulatus venom, BE.EP.DR

Abstract

Tityus serrulatus is considered the most dangerous scorpion in Brazil, being responsible for most severe cases of scorpion envenoming. The venom of T. serrulatus presents in its composition: nucleotide, insoluble mucus, mucopolysaccharides, oligopeptide, low molecular weight molecules, protease inhibitors, histamine releasers, amino acids and other organic compounds. Additionally the venom contains numerous low molecular weight proteins with neurotoxic activity of great importance to understand the functioning of ion channels and neuroexcitable phenomena. Its toxins have been extensively studied and many of them have been isolated and characterized. However, it is estimated by mass spectrometry data (unpublished data of the group) that the number of toxins to be described is much higher than those previously characterized. Recently, a study by the group found evidence of a new toxin present in the fraction VIB from Tityus serrulatus venom. Thus, this study aims to isolate and characterize structurally (amino acid sequence) and functionally this new toxin. For the functional characterization of the novel toxin will be performed electrophysiological tests on sodium and/or potassium voltage-dependent channels cloned and expressed in oocytes, immunoassays of cytokine release in vitro and biochemical determinations of glucose, AST, ALT , CK, urea and plasma creatinine in vivo. The study of toxins from scorpion venom has been shown relevant for providing the molecular basis involved in the mechanism of its toxicity and identify molecules with potential use as drugs or as tools for studies of different biological systems.

Scientific publications

(13)

(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)

PUCCA, MANUELA B.; BERTOLINI, THAIS B.; CERNI, FELIPE A.; BORDON, KARLA C. F.; PEIGNEUR, STEVE; TYTGAT, JAN; BONATO, VANIA L.; ARANTES, ELIANE C.. Immunosuppressive evidence of Tityus serrulatus toxins Ts6 and Ts15: insights of a novel K+ channel pattern in T cells. Immunology, v. 147, n. 2, p. 240-250, FEB 2016. (12/12954-6, 13/21342-7, 13/21329-0, 12/13590-8)

PUCCA, MANUELA BERTO; CERNI, FELIPE AUGUSTO; PINHEIRO-JUNIOR, ERNESTO LOPES; ZOCCAL, KARINA FURLANI; FIGUEIREDO BORDON, KARLA DE CASTRO; AMORIM, FERNANDA GOBBI; PEIGNEUR, STEVE; VRIENS, KIM; THEVISSEN, KARIN; ANGELO CAMMUE, BRUNO PHILIPPE; et al. Non-disulfide-bridged peptides from Tityus serrulatus venom: Evidence for proline-free ACE-inhibitors. Peptides, v. 82, p. 44-51, AUG 2016. (13/21342-7, 14/03332-7, 12/13590-8, 13/06380-0, 14/07125-6, 13/21329-0, 11/12317-3)

CERNI, FELIPE A.; PUCCA, MANUELA B.; PEIGNEUR, STEVE; CREMONEZ, CAROLINE M.; BORDON, KARLA C. F.; TYTGAT, JAN; ARANTES, ELIANE C.. Electrophysiological Characterization of Ts6 and Ts7, K+ Channel Toxins Isolated through an Improved Tityus serrulatus Venom Purification Procedure. TOXINS, v. 6, n. 3, p. 892-913, MAR 2014. (08/10761-0, 12/13590-8)

BOLDRINI-FRANCA, JOHARA; COLOGNA, CAMILA TAKENO; PUCCA, MANUELA BERTO; FIGUEIREDO BORDON, KARLA DE CASTRO; AMORIM, FERNANDO GOBBI; PINO ANJOLETTE, FERNANDO ANTONIO; CORDEIRO, FRANCIELLE ALMEIDA; WIEZEL, GISELE ADRIANO; CERNI, FELIPE AUGUSTO; PINHEIRO-JUNIOR, ERNESTO LOPES; et al. Minor snake venom proteins: Structure, function and potential applications. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1861, n. 4, p. 824-838, APR 2017. (14/06170-8, 11/12317-3, 11/23236-4, 15/16714-8, 12/13590-8, 13/26619-7, 14/15644-3, 12/12954-6, 13/26200-6)

PUCCA, MANUELA BERTO; CERNI, FELIPE AUGUSTO; CORDEIRO, FRANCIELLE ALMEIDA; PEIGNEUR, STEVE; CUNHA, THIAGO MATTAR; TYTGAT, JAN; ARANTES, ELIANE CANDIANI. Ts8 scorpion toxin inhibits the Kv4.2 channel and produces nociception in vivo. Toxicon, v. 119, p. 244-252, SEP 1 2016. (12/12954-6, 13/21342-7, 12/13590-8, 13/21329-0, 13/08216-2)

LIMA, PRISCILA C.; BORDON, KARLA C. F.; PUCCA, MANUELA B.; CERNI, FELIPE A.; ZOCCAL, KARINA F.; FACCIOLI, LUCIA H.; ARANTES, ELIANE C.. Partial purification and functional characterization of Ts19 Frag-I, a novel toxin from Tityus serrulatus scorpion venom. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 21, DEC 1 2015. (12/12954-6, 12/13590-8)

PUCCA, MANUELA BERTO; AMORIM, FERNANDA GOBBI; CERNI, FELIPE ATIGUSTO; FIGUEIREDO BORDON, KARLA DE CASTRO; CARDOSO, IARA AIME; PINO ANJOLETTE, FERNANDO ANTONIO; ARANTES, ELIANE CANDIANI. Influence of post-starvation extraction time and prey-specific diet in Tityus serrulatus scorpion venom composition and hyaluronidase activity. Toxicon, v. 90, p. 326-336, NOV 2014. (12/12954-6, 11/12317-3, 12/13590-8)

CERNI, FELIPE AUGUSTO; PUCCA, MANUELA BERTO; AMORIM, FERNANDA GOBBI; FIGUEIREDO BORDON, KARLA DE CASTRO; ECHTERBILLE, JULIEN; QUINTON, LOIC; DE PAUW, EDWIN; PEIGNEUR, STEVE; TYTGAT, JAN; ARANTES, ELIANE CANDIANI. Isolation and characterization of Ts19 Fragment II, a new long-chain potassium channel toxin from Tityus serrulatus venom. Peptides, v. 80, p. 9-17, JUN 2016. (13/21342-7, 12/13590-8, 13/21329-0, 13/26083-0, 11/12317-3)

DE OLIVEIRA, GUILHERME HONDA; CERNI, FELIPE AUGUSTO; CARDOSO, IARA AIME; ARANTES, ELIANE CANDIANI; PUCCA, MANUELA BERTO. Tityus serrulatus envenoming in non-obese diabetic mice: a risk factor for severity. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 22, SEP 17 2016. (12/12954-6, 12/13590-8)

LODOVICHO, MARINA E.; COSTA, TASSIA R.; BERNARDES, CAROLINA P.; MENALDO, DANILO L.; ZOCCAL, KARINA F.; CARONE, SANTE E.; ROSA, JOSE C.; PUCCA, MANUELA B.; CERNI, FELIPE A.; ARANTES, ELIANE C.; et al. Investigating possible biological targets of Bj-CRP, the first cysteine-rich secretory protein (CRISP) isolated from Bothrops jararaca snake venom. Toxicology Letters, v. 265, p. 156-169, JAN 4 2017. (12/12954-6, 11/23236-4, 12/13590-8)

PUCCA, MANUELA BERTO; CEMI, FELIPE AUGUSTO; PINHEIRO JUNIOR, ERNESTO LOPES; FIGUEIREDO BORDON, KARLA DE CASTRO; AMORIM, FEMANDA GOBBI; CORDEIRO, FRANCIELLE ALMEIDA; LONGHIM, HELOISA TAVONI; CREMONEZ, CAROLINE MARRONI; OLIVEIRA, GUILHERME HONDA; ARANTES, ELIANE CANDIANI. Tityus serrulatus venom - A lethal cocktail. Toxicon, v. 108, p. 272-284, DEC 15 2015. (12/12954-6, 11/12317-3, 14/07824-1, 12/13590-8)

CREMONEZ, CAROLINE MARRONI; LEITE, FLAVIA PINE; FIGUEIREDO BORDON, KARLA DE CASTRO; CERNI, FELIPE AUGUSTO; CARDOSO, IARA AIME; DE OLIVEIRA GREGORIO, ZITA MARIA; GONCALVES DE SOUZA, RODRIGO CANCADO; DE SOUZA, ANA MARIA; ARANTES, ELIANE CANDIANI. Experimental Lachesis muta rhombeata envenomation and effects of soursop (Annona muricata) as natural antivenom. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 22, MAR 8 2016. (05/54855-0, 12/13590-8)

PUCCA, MANUELA B.; BERTOLINI, THAIS B.; CERNI, FELIPE A.; BORDON, KARLA C. F.; PEIGNEUR, STEVE; TYTGAT, JAN; BONATO, VANIA L.; ARANTES, ELIANE C.. Immunosuppressive evidence of Tityus serrulatus toxins Ts6 and Ts15: insights of a novel K+ channel pattern in T cells. IMMUNOLOGY, v. 147, n. 2, p. 11-pg., 2016-02-01. (12/12954-6, 13/21329-0, 13/21342-7, 12/13590-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CERNI, Felipe Augusto. Isolation, molecular and functional characterization of a new toxin present in the Tityus serrulatus scorpion venom. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.