| Mitochondrial-Targeted Plastoquinone Derivatives. Effect on Senescence and Acute Age-Related Pathologies. | |
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MedLine Citation:
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PMID: 21269268 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Plastoquinone, a very effective electron carrier and antioxidant of chloroplasts, was conjugated with decyltriphenylphosphonium to obtain a cation easily penetrating through membranes. This cation, called SkQ1, is specifically targeted to mitochondria by electrophoresis in the electric field formed by the mitochondrial respiratory chain. The respiratory chain also regenerates reduced SkQ1H2 from its oxidized form that appears as a result of the antioxidant activity of SkQ1H(2). SkQ1H(2) prevents oxidation of cardiolipin, a mitochondrial phospholipid that is especially sensitive to attack by reactive oxygen species (ROS). In cell cultures, SkQ1 and its analog plastoquinonyl decylrhodamine 19 (SkQR1) arrest H(2)O(2)-induced apoptosis. When tested in vivo, SkQs (i) prolong the lifespan of fungi, crustaceans, insects, fish, and mice, (ii) suppress appearance of a large number of traits typical for age-related senescence (cataract, retinopathies, achromotrichia, osteoporosis, lordokyphosis, decline of the immune system, myeloid shift of blood cells, activation of apoptosis, induction of β-galactosidase, phosphorylation of H2AX histones, etc.) and (iii) lower tissue damage and save the lives of young animals after treatments resulting in kidney ischemia, rhabdomyolysis, heart attack, arrhythmia, and stroke. We suggest that the SkQs reduce mitochondrial ROS and, as a consequence, inhibit mitochondria-mediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast "biochemical suicide" of an organism after a severe metabolic crisis. |
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Authors:
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M V Skulachev; Y N Antonenko; V N Anisimov; B V Chernyak; D A Cherepanov; V A Chistyakov; M V Egorov; N G Kolosova; G A Korshunova; K G Lyamzaev; E Y Plotnikov; V A Roginsky; I I Severina; F F Severin; T P Shkurat; V N Tashlitsky; K M Shidlovsky; M Y Vyssokikh; A A Zamyatnin; D B Zorov; V P Skulachev |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-1-26 |
Journal Detail:
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Title: Current drug targets Volume: - ISSN: 1873-5592 ISO Abbreviation: - Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-1-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100960531 Medline TA: Curr Drug Targets Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Vorobyevy Gory 1, Moscow 119991, Russia. skulach@belozersky.msu.ru. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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