In situ and in vitro analysis of nitric oxide, apoptosis and mitochondrial biogenesis in mitochondrial diseases and C2C12 myoblast cell line

• Grant number: 07/00808-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2008
• End date: August 31, 2011
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Célia Harumi Tengan
• Grantee: Gabriela Silva Rodrigues
• Host Institution: 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 the muscle biopsy of the patients with MD, generally, there is a histological modification characterized by the accumulation of structurally abnormal mitochondria in the muscular fiber (Ragged Red Fibers- RRF). This increase in the size and mitochondrial number is treated as a way to compensate the mitochondrial functional insufficiency, 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 in apoptosis. 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. A study enclosing the integrated analysis of these factors is important because there are therapeutical strategies (exercise therapy and L-arginine administration; NO precursor) that are applied in patients with MD although little is known about the exact influence of these factors. The objective of this study is to perform analyses by an in situ approach on muscle biopsy of patients with MD to address the relationship between Nitric Oxide Synthase (NOS) activity, mitochondrial function and proliferation (COX and SDH) and apoptosis. We will also analyze, by an in vitro approach, the treatment of culture of myoblasts (C2C12) with NO donor, NOS antagonist and the L-arginine and their relation with mithochondrial content and function. (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)