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Molecular mechanism for the selective impairment of cancer mitochondrial function by a mitochondrially targeted vitamin E analogue

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    0383182 - BTÚ 2013 RIV NL eng J - Článek v odborném periodiku
    Rodriguez-Enriquez, S. - Hernandez-Esquivel, L. - Marin-Hernandez, A. - Dong, L.-F. - Akporiaye, E. - Neužil, Jiří - Ralph, S.J. - Moreno-Sanchez, R.
    Molecular mechanism for the selective impairment of cancer mitochondrial function by a mitochondrially targeted vitamin E analogue.
    Biochimica Et Biophysica Acta-Bioenergetics. Roč. 1817, č. 9 (2012), s. 1597-1607. ISSN 0005-2728
    Grant CEP: GA ČR GAP301/10/1937
    Výzkumný záměr: CEZ:AV0Z50520701
    Klíčová slova: Mitochondria * respiratory complex II * vitamin E analogs
    Kód oboru RIV: CE - Biochemie
    Impakt faktor: 4.624, rok: 2012

    The effects of alpha-tocopheryl succinate (alpha-TOS), alpha-tocopheryl acetyl ether (alpha-TEA) and triphenylphosphonium-tagged vitamin E succinate (mitochondrially targeted vitamin E succinate; MitoVES) on energy-related mitochondrial functions were determined in mitochondria isolated from AS-30D hepatoma and rat liver, bovine heart sub-mitochondrial particles (SMPs), and in rodent and human carcinoma cell lines and rat hepatocytes. In isolated mitochondria, MitoVES stimulated basal respiration and ATP hydrolysis, but inhibited net state 3 (ADP-stimulated) respiration and Ca2+ uptake, by collapsing the membrane potential at low doses (1-10 mu M). Uncoupled mitochondrial respiration and basal respiration of SMPs were inhibited by the three drugs at concentrations at least one order of magnitude higher and with different efficacy: MitoVES> alpha-TEA>alpha-TOS. At high doses (>10 mu M), the respiratory complex II (CII) was the most sensitive MitoVES target. Acting as an uncoupler at low doses, this agent stimulated total O-2 uptake, collapsed Delta Psi(m), inhibited oxidative phosphorylation and induced ATP depletion in rodent and human cancer cells more potently than in normal rat hepatocytes. These findings revealed that in situ tumor mitochondria are preferred targets of the drug, indicating its clinical relevance. (C) 2012 Elsevier B.V. All rights reserved.
    Trvalý link: http://hdl.handle.net/11104/0213201
     
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