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Mechanistic insights on the effects of suramin, on the cardiomyopathy of the mdx mice

Grant number: 12/03498-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2012
Effective date (End): February 28, 2015
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Maria Julia Marques
Grantee:Drielen de Oliveira Moreira
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Duchenne Muscular Dystrophy (DMD) is a genetic disease characterized by the lack of dystrophin and progressive skeletal and cardiac muscles degeneration. In DMD and in the mdx mice model of DMD, heart and diaphragm are severely affected showing extensive fibrosis and loss of function. Cardiomyopathy is an increasing cause of death in DMD. However, while some drugs show positive effects in the function of the cardiac muscle, they may have no effect on cardiac fibrosis or on skeletal muscle dystrophy. Therefore, the study of new possibilities of pharmacological therapy is important.Previously, we demonstrated that suramin, an anti fibrotic agent used to treat some types of human cancer, was able to protect the dystrophic diaphragm and limb muscles of the mdx mice against myonecrosis (Taniguti et al., 2011). Further, we demonstrated that suramin improved the levels of b-dystroglycan, a key component of the dystrophin-glycoprotein complex (Taniguti et al., 2012, submitted). More recently, we demonstrated positive effects of suramin on mdx cardiomyopathy, by decreasing cardiac fibrosis and ameliorating mdx electrocardiography (Moreira et al., in preparation).In the present study, we aim to further evaluate the actions of suramin on the dystrophic cardiac muscle. First, we will verify whether suramin also affects b-dystroglycan levels. Second, we will evaluate the actions of suramin as a blocker of purinergic receptors, which are suggested to be involved in the cardiomyopathy related to other diseases.

Scientific publications
(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)
MOREIRA, DRIELEN DE OLIVEIRA; NETO, HUMBERTO SANTO; MARQUES, MARIA JULIA. P2Y(2) purinergic receptors are highly expressed in cardiac and diaphragm muscles of mdx mice, and their expression is decreased by suramin. MUSCLE & NERVE, v. 55, n. 1, p. 116-121, JAN 2017. Web of Science Citations: 3.
MARANHAO, JULIANA BARROS; MOREIRA, DRIELEN DE OLIVEIRA; MAURICIO, ADRIANA FOGAGNOLO; DE CARVALHO, SAMARA CAMACARI; FERRETTI, RENATO; PEREIRA, JULIANO ALVES; SANTO NETO, HUMBERTO; MARQUES, MARIA JULIA. Changes in calsequestrin, TNF-alpha, TGF-beta and MyoD levels during the progression of skeletal muscle dystrophy in mdx mice: a comparative analysis of the quadriceps, diaphragm and intrinsic laryngeal muscles. International Journal of Experimental Pathology, v. 96, n. 5, p. 285-293, OCT 2015. Web of Science Citations: 7.
MOREIRA, DRIELEN DE OLIVEIRA; PEREIRA, JULIANO ALVES; TIEMI TANIGUTI, ANA PAULA; MATSUMURA, CINTIA YURI; FERREIRA RAMOS, LUIS ALBERTO; AREAS, MIGUEL ARCANJO; NETO, HUMBERTO SANTO; MARQUES, MARIA JULIA. SURAMIN ATTENUATES DYSTROPHIN-DEFICIENT CARDIOMYOPATHY IN THE mdx MOUSE MODEL OF DUCHENNE MUSCULAR DYSTROPHY. MUSCLE & NERVE, v. 48, n. 6, p. 911-919, DEC 2013. Web of Science Citations: 4.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MOREIRA, Drielen de Oliveira. Action mechanisms of suramin on cardiomyopathy in the mdx mice. 2015. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.