Study of the relationship between nitric oxide synthesis, mitochondrial biogenesis and apoptosis in skeletal muscle

• Grant number: 07/03145-9
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2008
• End date: June 30, 2010
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Célia Harumi Tengan
• Grantee: Célia Harumi Tengan
• Host Institution: Departamento de Neurologia e Neurocirurgia. Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Mitochondrial Diseases (MD) are a heterogeneous group of diseases characterized by alterations of the mitochondrial metabolism that result, mainly, in nervous and muscular system impairment. In muscle biopsies of the patients with MD, there is a histological modification characterized by the accumulation of structurally abnormal mitochondria in muscle fibers (ragged red fibers- RRF). This increase in size and mitochondrial number is a way to compensate mitochondrial dysfunction, however, the mechanism underlying this process is not known. Some studies show that nitric oxide (NO) is involved in mitochondrial biogenesis in several cellular types and has a pro-apoptotic role. Moreover, other studies have shown apoptosis in RRF muscle fibers of patients with MD. However, no previous study has shown the relation between NO, mitochondrial proliferation and apoptosis in patients with MD. The objective of this study is (1) to perform an integrated analysis of NO synthase activity, mitochondrial function, proliferation, molecular defect and apoptosis; (2) evaluate mitochondrial content and function of myoblast cultures after treatment with an NO donor, NOS antagonist and L-arginine. NOS activity will be evaluated by NADPH diaphorase histochemisty, mitochondrial function by SDH and COX histochemistry, and apoptosis by the expression of activated caspase 3. Mitochondrial content and function of myoblasts will be evaluated by SDH histochemistry, fluorescent mitochondrial markers and expression of mitochondrial proteins by Western blot. (AU)

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)

RODRIGUES, GABRIELA SILVA; GODINHO, ROSELY OLIVEIRA; KIYOMOTO, BEATRIZ HITOMI; GAMBA, JULIANA; BULLE OLIVEIRA, ACARY SOUZA; SCHMIDT, BENY; TENGAN, CELIA HARUMI. Integrated analysis of the involvement of nitric oxide synthesis in mitochondrial proliferation, mitochondrial deficiency and apoptosis in skeletal muscle fibres. SCIENTIFIC REPORTS, v. 6, FEB 9 2016. (07/00808-7, 07/03145-9)