L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency.
Camila D S BarrosJomênica B LivramentoMargaret G MouroElisa Mieko Suemitsu HigaCarlos Torres MoraesCelia Harumi TenganPublished in: Nutrients (2021)
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.
Keyphrases
- oxidative stress
- induced apoptosis
- nitric oxide
- mitochondrial dna
- dna damage
- cell cycle arrest
- diabetic rats
- ischemia reperfusion injury
- endoplasmic reticulum stress
- signaling pathway
- amino acid
- copy number
- gene expression
- protein protein
- blood brain barrier
- high resolution
- endothelial cells
- cell proliferation
- cerebral blood flow
- smoking cessation
- single molecule
- atomic force microscopy