Inhibition of myocardial reperfusion injury by ischemic postconditioning requires sirtuin 3-mediated deacetylation of cyclophilin D.


RATIONALE:How ischemic postconditioning can inhibit opening of the mitochondrial permeability transition pore (PTP) and subsequent cardiac myocytes death at reperfusion remains unknown. Recent studies have suggested that de-acetylation of cyclophilin D (CyPD) by sirtuin 3 (SIRT3) can modulate its binding to the PTP. OBJECTIVE:The aim of the present study was to examine whether ischemic postconditioning (PostC) might activate SIRT3 and consequently prevent lethal myocardial reperfusion injury through a deacetylation of CyPD. METHODS AND RESULTS:Using hypoxia-reoxygenation (H/R) in H9C2 cells, we showed that SIRT3 overexpression prevented CyPD acetylation, limited PTP opening and reduced cell death by 24%. In vitro modification of the CyPD acetylation status in MEFs by site-directed mutagenesis altered capacity of PTP opening by calcium. Calcium Retention Capacity (CRC) was significantly decreased with CyPD-KQ that mimics acetylated protein compared with CyPD WT (871 ± 266 vs 1193 ± 263 nmoles Ca(2+)/mg protein respectively). Cells expressing non-acetylable CyPD mutant (CyPD-KR) displayed 20% decrease in cell death compared to cells expressing CyPD WT after H/R. Correspondingly, in mice we showed that cardiac ischemic postconditioning could not reduce infarct size and CyPD acetylation in SIRT3 KO mice, and was unable to restore CRC in mitochondria as it is observed in WT mice. CONCLUSIONS:Our study suggests that the increased acetylation of CyPD following myocardial ischemia-reperfusion facilitates PTP opening and subsequent cell death. Therefore ischemic postconditioning might prevent lethal reperfusion injury through an increased SIRT3 activity and subsequent attenuation of CyPD acetylation at reperfusion.


J Mol Cell Cardiol


Bochaton T,Crola-Da-Silva C,Pillot B,Villedieu C,Ferreras L,Alam MR,Thibault H,Strina M,Gharib A,Ovize M,Baetz D




Has Abstract


2015-07-01 00:00:00












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    authors: Liron T,Chen LE,Khaner H,Vallentin A,Mochly-Rosen D

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    pub_type: 杂志文章


    authors: Kitakaze M,Node K,Minamino T,Asanuma H,Ueda Y,Kosaka H,Kuzuya T,Hori M

    更新日期:1998-11-01 00:00:00

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    authors: Mosca SM,Gelpi RJ,Cingolani HE

    更新日期:1994-10-01 00:00:00

  • Ca2+/calmodulin-dependent protein kinase II is essential in hyperacute pressure overload.

    abstract:BACKGROUND:Activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) is established as a central intracellular trigger for various cardiac pathologies such as hypertrophy, heart failure or arrhythmias in animals and humans suggesting CaMKII as a promising target protein for future medical treatments. However, ...

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    authors: Baier MJ,Klatt S,Hammer KP,Maier LS,Rokita AG

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    authors: LaFramboise WA,Guthrie RD,Scalise D,Elborne V,Bombach KL,Armanious CS,Magovern JA

    更新日期:2003-10-01 00:00:00

  • Post-translational regulation of calsarcin-1 during pressure overload-induced cardiac hypertrophy.

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    authors: Paulsson AK,Franklin S,Mitchell-Jordan SA,Ren S,Wang Y,Vondriska TM

    更新日期:2010-06-01 00:00:00

  • Serine/Threonine Phosphatases in Atrial Fibrillation.

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    pub_type: 杂志文章,评审


    authors: Heijman J,Ghezelbash S,Wehrens XH,Dobrev D

    更新日期:2017-02-01 00:00:00

  • Characterization and expression of a heart-selective alternatively spliced variant of alpha II-spectrin, cardi+, during development in the rat.

    abstract::Spectrin is a large, flexible protein that stabilizes membranes and organizes proteins and lipids into microdomains in intracellular organelles and at the plasma membrane. Alternative splicing occurs in spectrins, but it is not yet clear if these small variations in structure alter spectrin's functions. Three alternat...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Zhang Y,Resneck WG,Lee PC,Randall WR,Bloch RJ,Ursitti JA

    更新日期:2010-06-01 00:00:00

  • Effect of alpha-tocopherol on high energy phosphate metabolite levels in rat heart by 31P-NMR using a Langendorff perfusion technique.

    abstract::To examine the action of alpha-tocopherol on high energy phosphate compounds, a 31P-NMR technique was applied to perfused Langendorff rat hearts. Rats were treated with tocopherol acetate (25 mg/kg body wt i.p.) for 7 consecutive days. On the 7th day, the rat hearts were isolated for the Langendorff experiment. After ...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Kotegawa M,Sugiyama M,Shoji T,Haramaki N,Ogura R

    更新日期:1993-09-01 00:00:00

  • Temperature affects human cardiac sarcoplasmic reticulum energy-mediated calcium transport.

    abstract::Hypothermic cardioplegic solutions are currently used to preserve cardiac function during transportation. However, it has been shown that end-diastolic compliance decreases in donor hearts during reperfusion. Excessively cold temperatures may affect membrane-bound enzymes (Ca2+ ATPase and Ca2+ uptake) which are necess...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Labow RS,Hendry PJ,Meek E,Keon WJ

    更新日期:1993-10-01 00:00:00

  • Differential protein expression profiling of myocardial tissue in a mouse model of hypertrophic cardiomyopathy.

    abstract::Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes encoding sarcomere proteins. The mechanisms involved in the development of cardiac hypertrophy and heart failure remain poorly understood. Global proteomic profiling was used to study the cardiac proteome of mice predisposed to develo...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Lam L,Tsoutsman T,Arthur J,Semsarian C

    更新日期:2010-05-01 00:00:00

  • Molecular mechanisms underlying the long-term impact of dietary fat to increase cardiac pyruvate dehydrogenase kinase: regulation by insulin, cyclic AMP and pyruvate.

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    authors: Sugden MC,Orfali KA,Fryer LG,Holness MJ,Priestman DA

    更新日期:1997-07-01 00:00:00

  • Beta-adrenergic receptor blockade modulates Bcl-X(S) expression and reduces apoptosis in failing myocardium.

    abstract::The mechanisms by which beta-adrenergic receptor (beta-AR) blockade modulates apoptosis in heart failure (HF) are unclear. We examined the impact of beta-AR blockade with metoprolol on myocardial remodeling, apoptosis, pro-apoptotic (Fas, Fas ligand, Bax, and Bcl-X(S)) and anti-apoptotic (Bcl-X(L)and Bcl-2) gene expre...

    journal_title:Journal of molecular and cellular cardiology

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    authors: Prabhu SD,Wang G,Luo J,Gu Y,Ping P,Chandrasekar B

    更新日期:2003-05-01 00:00:00

  • An analysis of lidocaine block of sodium current in isolated human atrial and ventricular myocytes.

    abstract::Lidocaine is a Na+ channel blocker that is highly effective for the treatment of ventricular tachyarrhythmias, but is largely ineffective against atrial arrhythmias. If is not known if this differential efficacy is the result of differences in lidocaine inhibition of atrial v ventricular Na+ channels. The purpose of t...

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    pub_type: 杂志文章


    authors: Furukawa T,Koumi S,Sakakibara Y,Singer DH,Jia H,Arentzen CE,Backer CL,Wasserstrom JA

    更新日期:1995-02-01 00:00:00

  • Quantitation of Na/Ca exchanger function in single ventricular myocytes.

    abstract::A Na/Ca exchange current can be elicited in voltage clamped single ventricular myocytes by the abrupt removal of extracellular Na+ by means of a rapid switcher device. We measured this reverse Na/Ca exchange current in isolated mouse ventricular myocytes from wild-type mice, and from transgenic mice with hearts overex...

    journal_title:Journal of molecular and cellular cardiology

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    authors: Su Z,Bridge JH,Philipson KD,Spitzer KW,Barry WH

    更新日期:1999-05-01 00:00:00

  • 'Calcium paradox' in the heart is modulated by cell sodium during the calcium-free period.

    abstract::We hypothesized that after a Ca2+-free period the magnitude of the Na+ gradient at the onset of Ca2+ reperfusion would grade the ensuing cell Ca2+ gain. Rabbit interventricular septa perfused with Hepes buffered solution (pH 7.4, [Ca2+] = 1.0 mM) and stimulated to contract isometrically at 60 min-1 at 30 degrees C wer...

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    authors: Ruaño-Arroyo G,Gerstenblith G,Lakatta EG

    更新日期:1984-09-01 00:00:00

  • Isoenzyme-specific protein kinase C and c-Jun N-terminal kinase activation by electrically stimulated contraction of neonatal rat ventricular myocytes.

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    authors: Strait JB,Samarel AM

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  • Ca(2+) influx through L-type Ca(2+) channels and transient receptor potential channels activates pathological hypertrophy signaling.

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    authors: Gao H,Wang F,Wang W,Makarewich CA,Zhang H,Kubo H,Berretta RM,Barr LA,Molkentin JD,Houser SR

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    authors: Lu CY,Giordano FJ,Rogers KC,Rothman A

    更新日期:1996-08-01 00:00:00

  • Dysfunction of cardiac ryanodine receptors in the metabolic syndrome.

    abstract::This study examined the hypothesis that the prediabetic metabolic syndrome alters expression, phosphorylation state and binding affinity of cardiac RyR2. Real-time PCR and Western blot analysis were used to assess mRNA and protein expression in the left ventricle, right ventricle and right atrium from control (n=5) an...

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    authors: Dincer UD,Araiza A,Knudson JD,Shao CH,Bidasee KR,Tune JD

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  • PDGF-BB enhances monocyte chemoattractant protein-1 mRNA stability in smooth muscle cells by downregulating ribonuclease activity.

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    authors: Liu B,Poon M,Taubman MB

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  • In vivo expression of a conditional TGF-beta1 transgene: no evidence for TGF-beta1 transgene expression in SM22alpha-tTA transgenic mice.

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    authors: Lee S,Agah R,Xiao M,Frutkin AD,Kremen M,Shi H,Dichek DA

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    authors: Herzum M,Weller R,Jomaa H,Wietrzychowski F,Pankuweit S,Mahr P,Maisch B

    更新日期:1995-08-01 00:00:00

  • Endothelium-targeted overexpression of constitutively active FGF receptor induces cardioprotection in mice myocardial infarction.

    abstract::Fibroblast growth factor receptor (FGFR) is expressed in a variety of cells and is involved in their proliferation/migration/survival. To elucidate FGFR-mediated specific action of vascular endothelial cells (ECs) on myocardial ischemia, we generated endothelium-targeted transgenic mice overexpressing constitutively a...

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    authors: Matsunaga S,Okigaki M,Takeda M,Matsui A,Honsho S,Katsume A,Kishita E,Che J,Kurihara T,Adachi Y,Mansukhani A,Kobara M,Matoba S,Tatsumi T,Matsubara H

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    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Sakai M,Danziger RS,Staddon JM,Lakatta EG,Hansford RG

    更新日期:1989-12-01 00:00:00

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    authors: Ito T,Kimura Y,Uozumi Y,Takai M,Muraoka S,Matsuda T,Ueki K,Yoshiyama M,Ikawa M,Okabe M,Schaffer SW,Fujio Y,Azuma J

    更新日期:2008-05-01 00:00:00

  • Nitric oxide-dependent vasodilation maintains blood flow in true hibernating myocardium.

    abstract::Patients with chronic coronary artery disease may exhibit chronically depressed regional myocardial function, which can be reversed by revascularization. This was called hibernating myocardium, since it was thought that myocardial blood flow was also chronically reduced and since animals during true hibernation are th...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Kudej RK,Vatner SF

    更新日期:2003-08-01 00:00:00

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    abstract::In the present investigation, the effects of forskolin on intracellular sodium activity were studied in quiescent and electrically stimulated cardiac Purkinje fibers from sheep using Na+-sensitive microelectrodes. Also assessed, were the effects of this promoter of cytosolic cAMP production on resting membrane potenti...

    journal_title:Journal of molecular and cellular cardiology

    pub_type: 杂志文章


    authors: Zalups RK,Sheu SS

    更新日期:1987-09-01 00:00:00

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    authors: Mika D,Bobin P,Lindner M,Boet A,Hodzic A,Lefebvre F,Lechène P,Sadoune M,Samuel JL,Algalarrondo V,Rucker-Martin C,Lambert V,Fischmeister R,Vandecasteele G,Leroy J

    更新日期:2019-08-01 00:00:00