{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:43:24Z","timestamp":1781073804504,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T00:00:00Z","timestamp":1612569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/22574-0"],"award-info":[{"award-number":["2017\/22574-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Finance Code 001"],"award-info":[{"award-number":["Finance Code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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&gt;G). We evaluated mitochondrial enzyme activity, mitochondrial mass, NO concentration, and nitro-oxidative stress. Our results showed that m.3243A&gt;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&gt;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.<\/jats:p>","DOI":"10.3390\/nu13020534","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T02:08:12Z","timestamp":1613268492000},"page":"534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency"],"prefix":"10.3390","volume":"13","author":[{"given":"Camila D. S.","family":"Barros","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, Sao Paulo 04039-032, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3724-6288","authenticated-orcid":false,"given":"Jom\u00eanica B.","family":"Livramento","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, Sao Paulo 04039-032, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret G.","family":"Mouro","sequence":"additional","affiliation":[{"name":"Emergency and Nephrology Division, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo 04039-032, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa Mieko Suemitsu","family":"Higa","sequence":"additional","affiliation":[{"name":"Emergency and Nephrology Division, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo 04039-032, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8077-7092","authenticated-orcid":false,"given":"Carlos T.","family":"Moraes","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia Harumi","family":"Tengan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Universidade Federal de S\u00e3o Paulo, Sao Paulo 04039-032, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1146\/annurev.pharmtox.41.1.79","article-title":"The clinical pharmacology of L-arginine","volume":"41","year":"2001","journal-title":"Annu. 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