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Evaluation of the relationship between protein nitration and mitochondrial abnormalities

Grant number: 17/22574-0
Support Opportunities:Regular Research Grants
Start date: April 01, 2018
End date: September 30, 2020
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Célia Harumi Tengan
Grantee:Célia Harumi Tengan
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Nitric oxide is a free radical that interested several areas of research in medicine because it is involved in the pathogenesis of different diseases such as cardiovascular, respiratory, neurodegenerative, infectious diseases and cancer. One of the main actions of nitric oxide in mitochondria is the inhibitory effect on the respiratory chain, acting in the control of mitochondrial function. However, the inhibition in different sites in the respiratory chain can also lead to increased oxygen and nitrogen reactive species with further oxidative and nitrative stress. On the other hand, redox reactions induced by nitric oxide are not always deleterious, as they can also be important in the regulation of reactive species concentration or act in cell signaling. Previous work of our group have demonstrated that nitric oxide synthesis is altered in skeletal muscle of patients with mitochondrial deficiency and in cells with high proportions of mutated mitochondrial DNA. Our preliminary results suggest that there is protein nitration in these samples, however the pattern and amounts are variable. Thus, the objective of this project is to evaluate the relevance of protein nitration in mitochondrial deficiency of genetic origin. We will evaluate whether the presence of protein nitration is related to genotype or phenotype of patients with mitochondrial diseases and whether this alteration leads to worsening of mitochondrial function or is only a response to mitochondrial deficiency. The clarification of the relevance of protein nitration in mitochondrial diseases will help to improve treatment strategies based on the use of antioxidants for mitochondrial deficiencies. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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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)
BARROS, CAMILA D. S.; LIVRAMENTO, JOMENICA B.; MOURO, MARGARET G.; HIGA, ELISA MIEKO SUEMITSU; MORAES, CARLOS T.; TENGAN, CELIA HARUMI. L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency. NUTRIENTS, v. 13, n. 2, . (17/22574-0)
DE OLIVEIRA, MANUELLA GALVAO; TENGAN, CELIA; MICHELETTI, CECILIA; DE MACEDO, PALOMA RAMOS; SOARES PINHO CERNACH, MIRLENE CECILIA; CAVOLE, THIAGO RODRIGUES; BASTO, MARINA DE FRANCA; SOBREIRA FILHO, JOSELITO; VIRMOND, LUIZA AMARAL; MILANEZI, FERNANDA; et al. A novel variant in the COX15 gene causing a fatal infantile cardioencephalomyopathy: A case report with clinical and molecular review. EUROPEAN JOURNAL OF MEDICAL GENETICS, v. 64, n. 5, . (17/22574-0)