TY - JOUR
T1 - L-arginine reduces nitro-oxidative stress in cultured cells with mitochondrial deficiency
AU - Barros, Camila D.S.
AU - Livramento, Jomênica B.
AU - Mouro, Margaret G.
AU - Higa, Elisa Mieko Suemitsu
AU - Moraes, Carlos T.
AU - Tengan, Celia Harumi
N1 - Funding Information:
Funding: This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; processo no. 2017/22574-0), and in part by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001; CDSB and JBL were supported by scholarships from CAPES and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Funding Information:
This study was supported by Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo (FAPESP; processo no. 2017/22574-0), and in part by Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior?Brasil (CAPES)?Finance Code 001; CDSB and JBL were supported by scholarships from CAPES and Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2
Y1 - 2021/2
N2 - L-Arginine (L-ARG) supplementation has been suggested as a therapeutic option in several diseases, including Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS), arguably the most common mitochondrial disease. It is suggested that L-ARG, a nitric oxide (NO) precursor, can restore NO levels in blood vessels, improving cerebral blood flow. However, NO also participates in mitochondrial processes, such as mitochondrial biogenesis, the regulation of the respiratory chain, and oxidative stress. This study investigated the effects of L-ARG on mitochondrial function, nitric oxide synthesis, and nitro-oxidative stress in cell lines harboring the MELAS mitochondrial DNA (mtDNA) mutation (m.3243A>G). We evaluated mitochondrial enzyme activity, mitochondrial mass, NO concentration, and nitro-oxidative stress. Our results showed that m.3243A>G cells had increased NO levels and protein nitration at basal conditions. Treatment with L-ARG did not affect the mitochondrial function and mass but reduced the intracellular NO concentration and nitrated proteins in m.3243A>G cells. The same treatment led to opposite effects in control cells. In conclusion, we showed that the main effect of L-ARG was on protein nitration. Lowering protein nitration is probably involved in the mechanism related to L-ARG supplementation benefits in MELAS patients.
AB - L-Arginine (L-ARG) supplementation has been suggested as a therapeutic option in several diseases, including Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS), arguably the most common mitochondrial disease. It is suggested that L-ARG, a nitric oxide (NO) precursor, can restore NO levels in blood vessels, improving cerebral blood flow. However, NO also participates in mitochondrial processes, such as mitochondrial biogenesis, the regulation of the respiratory chain, and oxidative stress. This study investigated the effects of L-ARG on mitochondrial function, nitric oxide synthesis, and nitro-oxidative stress in cell lines harboring the MELAS mitochondrial DNA (mtDNA) mutation (m.3243A>G). We evaluated mitochondrial enzyme activity, mitochondrial mass, NO concentration, and nitro-oxidative stress. Our results showed that m.3243A>G cells had increased NO levels and protein nitration at basal conditions. Treatment with L-ARG did not affect the mitochondrial function and mass but reduced the intracellular NO concentration and nitrated proteins in m.3243A>G cells. The same treatment led to opposite effects in control cells. In conclusion, we showed that the main effect of L-ARG was on protein nitration. Lowering protein nitration is probably involved in the mechanism related to L-ARG supplementation benefits in MELAS patients.
KW - Arginine
KW - Mitochon-drial DNA
KW - Mitochondrial disease
KW - Nitration
KW - Nitric oxide
KW - Oxidative stress
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U2 - 10.3390/nu13020534
DO - 10.3390/nu13020534
M3 - Article
C2 - 33562042
AN - SCOPUS:85100478910
VL - 13
SP - 1
EP - 13
JO - Nutrients
JF - Nutrients
SN - 2072-6643
IS - 2
M1 - 534
ER -