Study of the toxins Ts6 e Ts15 from the scorpion Tityus serrulatus as potential therapeutic drugs for the treatment of autoimmune diseases

• Grant number: 12/12954-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2012
• End date: July 17, 2016
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Eliane Candiani Arantes Braga
• Grantee: Manuela Berto Pucca
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 13/21329-0 - Electrophysiological characterization of Tityus serrulatus venom toxins Ts3, Ts4, Ts6, Ts8, Ts15 and TS venom peptide 7: looking for new desired drugs, BE.EP.PD

Abstract

The potassium channel subtype Kv1.3 has been focus of scientific research, since it can be used as target for induction of T cell suppression since 1984. The mechanism by which Kv1.3 channels trigger immunossupression is directly related to intracellular calcium signaling. Therefore, in the absence of sufficient Ca2+ influx, the T cell activation, proliferation and effector functions are completely impaired. Thus, many diseases related to uncontrolled T cell response could be treated by blocking Kv1.3 channels and hence the influx of intracellular Ca2+. Currently, several animal toxins specific for Kv1.3 have demonstrated immunosuppressive effect for many diseases caused by T cells as delayed type hypersensibility, arthritis, multiple sclerosis, contact dermatitis, diabetes type I, II and obesity. The toxins Ts6 and Ts7 from the venom of Tityus serrulatus scorpion have been characterized electrophysiologically and shown to be specific for Kv 1.2 and Kv 1.3 channels, showing IC50 concentrations of nanomolar. Based on these results, Ts6 and Ts7 could be considered promising toxins for use in the treatment of diseases triggered by an unwanted T cell response. However, until now, these toxins have not been evaluated by functional tests to prove their possible therapeutic actions. In this context, this work will purify both toxins, Ts6 and Ts7, to evaluate them by functional in vitro and in vivo immunosuppressant assays of T cell , in particular using the multiple sclerosis animal model.

Scientific publications

(10)

(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)

PESSENDA, GABRIELA; SILVA, LUCIANO C.; CAMPOS, LUCAS B.; PACELLO, ELENICE M.; PUCCA, MANUELA B.; MARTINEZ, EDSON Z.; BARBOSA, JOSE E.. Human scFv antibodies (Afribumabs) against Africanized bee venom: Advances in melittin recognition. Toxicon, v. 112, p. 59-67, MAR 15 2016. (12/12954-6)

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)

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)

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)