Source:http://linkedlifedata.com/resource/pubmed/id/21167961
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2011-4-12
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pubmed:abstractText |
We studied the functional properties of isolated brain mitochondria (BM) prepared from total rat brain (BM(total)) or from cerebral subregions under basal and Ca(2+) overload conditions in order to evaluate the effects of cyclosporine A (CsA) in a regiospecific manner. CsA-induced effects were compared with those of two derivatives-the none-immunosuppressive [O-(NH(2)(CH2)(5)NHC(O)CH(2))-D-Ser](8)-CsA (Cs9) and its congener, the immunosuppressive [D-Ser](8)-CsA. The glutamate/malate-dependent state 3 respiration of mitochondria (state 3(glu/mal)) differed in region-specific manner (cortex > striatum = cerebellum > substantia nigra > hippocampus), but was significantly increased by 1?M CsA (+21±5%) in all regions. Ca(2+) overload induced by addition of 20?M Ca(2+) caused a significant decrease of state 3(glu/mal) (-45 to -55%) which was almost completely prevented in the presence of 1?M CsA, 1?M Cs9 or 1?M [D-Ser](8)-CsA. Mitochondrial Ca(2+) accumulation thresholds linked to permeability transition (PT) as well as the rate and completeness of mitochondrial Ca(2+) accumulation differed between different brain regions. For the first time, we provide a detailed, regiospecific analysis of Ca(2+)-dependent properties of brain mitochondria. Regardless of their immunosuppressive impact, CsA and its analogues improved mitochondrial functional properties under control conditions. They also preserved brain mitochondria against Ca(2+) overload-mediated PT and functional impairments. Since Cs9 does not mediate immunosuppression, it might be used as a more specific PT inhibitor than CsA.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1872-8278
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pubmed:author |
pubmed-author:FischerGunterG,
pubmed-author:GaynutdinovTimur MTM,
pubmed-author:GellerichFrank NFN,
pubmed-author:GizatullinaZemfira ZZZ,
pubmed-author:HeinzeHans-JochenHJ,
pubmed-author:JerzembekDoreenD,
pubmed-author:KnabeAnnetteA,
pubmed-author:MalesevicMiroslavM,
pubmed-author:StriggowFrankF,
pubmed-author:SvobodaHannoH,
pubmed-author:VielhaberStefanS
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
421-9
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pubmed:meshHeading |
pubmed-meshheading:21167961-Animals,
pubmed-meshheading:21167961-Brain,
pubmed-meshheading:21167961-Calcium,
pubmed-meshheading:21167961-Cell Respiration,
pubmed-meshheading:21167961-Cyclosporine,
pubmed-meshheading:21167961-Energy Metabolism,
pubmed-meshheading:21167961-Enzyme Inhibitors,
pubmed-meshheading:21167961-Male,
pubmed-meshheading:21167961-Mitochondria,
pubmed-meshheading:21167961-Rats
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pubmed:year |
2011
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pubmed:articleTitle |
Effects of cyclosporine A and its immunosuppressive or non-immunosuppressive derivatives [D-Ser]8-CsA and Cs9 on mitochondria from different brain regions.
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pubmed:affiliation |
Leibniz Institute for Neurobiology, Department Behavioral Neurology, Brenneckestr. 6, D-39118 Magdeburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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