PMID: identifiant
de la référence Pubmed : |
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 (22542467) |
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| titre : |
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Cardiac H11 kinase/Hsp22 stimulates oxidative phosphorylation and modulates mitochondrial reactive oxygen species production: Involvement of a nitric oxide-dependent mechanism. |
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| auteur(s) : |
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Lydie Laure1, Romain Long1, Paulo Lizano2, Roland Zini1, Alain Berdeaux1, Christophe Depré2, Didier Morin ( ) 1 |
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| laboratoire : |
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| résumé : |
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H11 kinase/Hsp22 (Hsp22), a small heat shock protein upregulated by ischemia/reperfusion, provides cardioprotection equal to ischemic preconditioning (IPC) through a nitric oxide (NO)-dependent mechanism. A main target of NO-mediated preconditioning is the mitochondria, where NO reduces O(2) consumption and reactive oxygen species (ROS) production during ischemia. Therefore, we tested the hypothesis that Hsp22 overexpression modulates mitochondrial function through an NO-sensitive mechanism. In cardiac mitochondria isolated from transgenic (TG) mice with cardiac-specific overexpression of Hsp22, mitochondrial basal, ADP-dependent, and uncoupled O(2) consumption was increased in the presence of either glucidic or lipidic substrates. This was associated with a decrease in the maximal capabilities of complexes I and III to generate superoxide anion in combination with an inhibition of superoxide anion production by the reverse electron flow. NO synthase expression and NO production were increased in mitochondria from TG mice. Hsp22-induced increase in O(2) consumption was abolished either by pretreatment of TG mice with the NO synthase inhibitor l-N(G)-nitroarginine methyl ester (l-NAME) or in isolated mitochondria by the NO scavenger phenyltetramethylimidazoline-1-oxyl-3-oxide. l-NAME pretreatment also restored the reverse electron flow. After anoxia, mitochondria from TG mice showed a reduction in both oxidative phosphorylation and H(2)O(2) production, an effect partially reversed by l-NAME. Taken together, these results demonstrate that Hsp22 overexpression increases the capacity of mitochondria to produce NO, which stimulates oxidative phosphorylation in normoxia and decreases oxidative phosphorylation and reactive oxygen species production after anoxia. Such characteristics replicate those conferred by IPC, thereby placing Hsp22 as a potential tool for prophylactic protection of mitochondrial function during ischemia. |
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| domaine : |
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Sciences du Vivant/Biochimie, Biologie Moléculaire
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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1873-4596 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1016/j.freeradbiomed.2012.03.001 |
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| journal : |
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Free Radic Biol Med |
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| Audience : |
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internationale |
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| date de publication : |
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01/06/2012 |
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date de publication
électronique : |
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18/04/2012 |
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| volume : |
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52 |
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| numéro : |
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11-12 |
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| page, identifiant, ... : |
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2168-76 |
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| mots-clés auteur : |
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H11 Kinase – heart – heat shock protein – mitochondria – nitric oxide – oxidative phosphorylation – reactive oxygen species |
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| contrat, financement : |
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L. Laure was supported by a post-doctoral grant from INSERM/AREMCAR. R. Long was supported by a doctoral grant from the Ministère de la Recherche et de la Technologie |
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