{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T20:18:11Z","timestamp":1780345091177,"version":"3.54.1"},"reference-count":45,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,10,15]]},"abstract":"<jats:p>Reactive nitrogen and oxygen species (O2\u2022\u2212, H2O2, NO\u2022 and ONOO\u2212) have been strongly implicated in the pathophysiology of neurodegenerative and mitochondrial diseases. In the present study, we examined the effects of nitrosative and\/or nitrative stress generated by DETA-NO {(Z)-1-[2-aminoethyl-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate}, SIN-1 (3-morpholinosydnonimine hydrochloride) and SNP (sodium nitroprusside) on U87MG glioblastoma cybrids carrying wt (wild-type) and mutant [A3243G (Ala3243\u2192Gly)] mtDNA (mitochondrial genome) from a patient suffering from MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). The mutant cybrids had reduced activity of cytochrome c oxidase, significantly lower ATP level and decreased mitochondrial membrane potential. However, endogenous levels of reactive oxygen species were very similar in all cybrids regardless of whether they carried the mtDNA defects or not. Furthermore, the cybrids were insensitive to the nitrosative and\/or nitrative stress produced by either DETA-NO or SIN-1 alone. Cytotoxicity, however, was observed in response to SNP treatment and a combination of SIN-1 and glucose-deprivation. The mutant cybrids were significantly more sensitive to these insults compared with the wt controls. Ultrastructural examination of dying cells revealed several characteristic features of autophagic cell death. We concluded that nitrosative and\/or nitrative stress alone were insufficient to trigger cytotoxicity in these cells, but cell death was observed with a combination of metabolic and nitrative stress. The vulnerability of the cybrids to these types of injury correlated with the cellular energy status, which were compromised by the MELAS mutation.<\/jats:p>","DOI":"10.1042\/bj20050272","type":"journal-article","created":{"date-parts":[[2006,2,6]],"date-time":"2006-02-06T10:17:48Z","timestamp":1139221068000},"page":"191-202","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Effects of nitric oxide donors on cybrids harbouring the mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) A3243G mitochondrial DNA mutation"],"prefix":"10.1042","volume":"391","author":[{"given":"Jagdeep\u00a0K.","family":"Sandhu","sequence":"first","affiliation":[{"name":"Neurogenesis and Brain Repair Group, M54, Institute for Biological Sciences, National Research Council Canada, 1200 Montreal Road, Ottawa, ON, Canada K1A 0R6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Sodja","sequence":"additional","affiliation":[{"name":"Neurogenesis and Brain Repair Group, M54, Institute for Biological Sciences, National Research Council Canada, 1200 Montreal Road, Ottawa, ON, Canada K1A 0R6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevan","family":"Mcrae","sequence":"additional","affiliation":[{"name":"Neurogenesis and Brain Repair Group, M54, Institute for Biological Sciences, National Research Council Canada, 1200 Montreal Road, Ottawa, ON, Canada K1A 0R6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Neurogenesis and Brain Repair Group, M54, Institute for Biological Sciences, National Research Council Canada, 1200 Montreal Road, Ottawa, ON, Canada K1A 0R6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rippstein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The Ottawa Hospital-Civic Campus, Ottawa, ON, Canada K1Y 4E9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yau-Huei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boleslaw","family":"Lach","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fay","family":"Lee","sequence":"additional","affiliation":[{"name":"Health Canada, Banting Research Center, Ottawa, ON, Canada K1A 0L2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Septimiu","family":"Bucurescu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary-Ellen","family":"Harper","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada K1H 8M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Sikorska","sequence":"additional","affiliation":[{"name":"Neurogenesis and Brain Repair Group, M54, Institute for Biological Sciences, National Research Council Canada, 1200 Montreal Road, Ottawa, ON, Canada K1A 0R6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2005,10,10]]},"reference":[{"key":"2021112213130200600_B1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/ana.410160409","article-title":"Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome","volume":"16","author":"Pavlakis","year":"1984","journal-title":"Ann. 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