Abstract：
:Heart failure is associated with mitochondrial dysfunction so that restoring or improving mitochondrial health is of therapeutic importance. Recently, reduction in NAD+ levels and NAD+-mediated deacetylase activity has been recognized as negative regulators of mitochondrial function. Using a cardiac specific KLF4 deficient mouse line that is sensitive to stress, we found mitochondrial protein hyperacetylation coupled with reduced Sirt3 and NAD+ levels in the heart before stress, suggesting that the KLF4-deficient heart is predisposed to NAD+-associated defects. Further, we demonstrated that short-term administration of Nicotinamide Mononucleotide (NMN) successfully protected the mutant mice from pressure overload-induced heart failure. Mechanically, we showed that NMN preserved mitochondrial ultrastructure, reduced ROS and prevented cell death in the heart. In cultured cardiomyocytes, NMN treatment significantly increased long-chain fatty acid oxidation despite no direct effect on pyruvate oxidation. Collectively, these results provide cogent evidence that hyperacetylation of mitochondrial proteins is critical in the pathogenesis of cardiac disease and that administration of NMN may serve as a promising therapy.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Zhang R,Shen Y,Zhou L,Sangwung P,Fujioka H,Zhang L,Liao Xdoi
10.1016/j.yjmcc.2017.09.001subject
Has Abstractpub_date
2017-11-01 00:00:00pages
64-73eissn
0022-2828issn
1095-8584pii
S0022-2828(17)30303-6journal_volume
112pub_type
杂志文章abstract：:Atrial fibrillation (AF) is commonly associated with chronic dilatation of the left atrium, both in human disease and animal models. The immediate signaling enzyme phospholipase C (PLC) is activated by mechanical stretch to generate the Ca2+-releasing messenger inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) and sn-1,2-di...
journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
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更新日期：2011-02-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
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doi：10.1016/s0022-2828(84)80642-2
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
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更新日期：2020-11-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
doi：10.1016/s0022-2828(84)80711-7
更新日期：1984-01-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2000.1116
更新日期：2000-05-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1996.0067
更新日期：1996-04-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2005.03.023
更新日期：2005-07-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.2001.1390
更新日期：2001-06-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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pub_type： 杂志文章
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更新日期：2009-11-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章,评审
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1016/j.yjmcc.2006.09.011
更新日期：2007-02-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1997.0458
更新日期：1997-08-01 00:00:00
abstract：:Studies using chemically-induced models of diabetes have shown the diabetic myocardium to exhibit abnormalities in cellular ion transport, which may affect susceptibility to reperfusion-induced arrhythmias. We studied the incidence of reperfusion-induced ventricular tachycardia (VT) and fibrillation (VF) in isolated h...
journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
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