AMPK in Cardiovascular Diseases

Daskalopoulos, Evangelos-Panagiotis; Dufeys, Cécile; Beauloye, Christophe; Bertrand, Luc; Horman, Sandrine

doi:10.1007/978-3-319-43589-3_8

Cited by 28 publications

(23 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(e) IHC staining for p-AMPK and p-mTOR. Scale bar represents 100 μm AMPK signalling plays a major role in various physiological and pathological cellular events that occur in cardiovascular diseases (Daskalopoulos, Dufeys, Beauloye, Bertrand, & Horman, 2016). AMPK is one of the master checkpoints of cellular metabolism and promotes autophagy by inhibiting mTOR (Ha & Kim, 2016).…”

Section: Discussionmentioning

confidence: 99%

Spermidine‐enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway

Yan

Wang

Ling

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

Background and Purpose Spermidine, a natural polyamine, is abundant in mammalian cells and is involved in cell growth, proliferation, and regeneration. Recently, oral spermidine supplements were cardioprotective in age‐related cardiac dysfunction, through enhancing autophagic flux. However, the effect of spermidine on myocardial injury and cardiac dysfunction following myocardial infarction (MI) remains unknown. Experimental Approach We determined the effects of spermidine in a model of MI, Sprague–Dawley rats with permanent ligation of the left anterior descending artery, and in cultured neonatal rat cardiomyocytes (NRCs) exposed to angiotensin II (Ang II). Cardiac function in vivo was assessed with echocardiography. In vivo and in vitro studies used histological and immunohistochemical techniques, along with western blots. Key Results Spermidine improved cardiomyocyte viability and decreased cell necrosis in NRCs treated with angiotensin II. In rats post‐MI, spermidine reduced infarct size, improved cardiac function, and attenuated myocardial hypertrophy. Spermidine also suppressed the oxidative damage and inflammatory cytokines induced by MI. Moreover, spermidine enhanced autophagic flux and decreased apoptosis both in vitro and in vivo. The protective effects of spermidine on cardiomyocyte apoptosis and cardiac dysfunction were abolished by the autophagy inhibitor chloroquine, indicating that spermidine exerted cardioprotective effects at least partly through promoting autophagic flux, by activating the AMPK/mTOR signalling pathway. Conclusions and Implications Our findings suggest that spermidine improved MI‐induced cardiac dysfunction by promoting AMPK/mTOR‐mediated autophagic flux.

show abstract

Section: Discussionmentioning

confidence: 99%

Spermidine‐enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway

Yan

Wang

Ling

et al. 2019

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…AMPK plays critical roles in numerous aspects of physiology ( 4 , 5 , 35 ) and is an important target for the treatment of metabolic diseases, including diabetes and obesity ( 1 , 7 ), as well as cancer ( 2 , 6 , 36 ) and heart disease ( 37 ). In addition, AMPK activation mimics many of the beneficial effects of exercise and caloric restriction ( 38 – 41 ).…”

Section: Discussionmentioning

confidence: 99%

Deconvoluting AMP-activated protein kinase (AMPK) adenine nucleotide binding and sensing

Yan

Novick

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

AMP-activated protein kinase (AMPK) is a central cellular energy sensor that adapts metabolism and growth to the energy state of the cell. AMPK senses the ratio of adenine nucleotides (adenylate energy charge) by competitive binding of AMP, ADP, and ATP to three sites (CBS1, CBS3, and CBS4) in its γ-subunit. Because these three binding sites are functionally interconnected, it remains unclear how nucleotides bind to individual sites, which nucleotides occupy each site under physiological conditions, and how binding to one site affects binding to the other sites. Here, we comprehensively analyze nucleotide binding to wild-type and mutant AMPK protein complexes by quantitative competition assays and by hydrogen-deuterium exchange MS. We also demonstrate that NADPH, in addition to the known AMPK ligand NADH, directly and competitively binds AMPK at the AMP-sensing CBS3 site. Our findings reveal how AMP binding to one site affects the conformation and adenine nucleotide binding at the other two sites and establish CBS3, and not CBS1, as the high affinity exchangeable AMP/ADP/ATP-binding site. We further show that AMP binding at CBS4 increases AMP binding at CBS3 by 2 orders of magnitude and reverses the AMP/ATP preference of CBS3. Together, these results illustrate how the three CBS sites collaborate to enable highly sensitive detection of cellular energy states to maintain the tight ATP homeostastis required for cellular metabolism.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Mammalian AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase containing a catalytic α subunit and regulatory β and γ subunits [ 7 ]. AMPK exerts protective effects against cardiac hypertrophy and heart failure [ 7–9 ]. Our previous studies have demonstrated that AMPK can attenuate cardiac hypertrophy induced by pressure overload or phenylephrine (PE) by blocking various signaling pathways, including nuclear factor of activated T cells (NFAT), MAPK, NF-κB, FOXO, and MuRF1 [ 10–12 ].…”

Section: Introductionmentioning

confidence: 99%

AMPK blunts chronic heart failure by inhibiting autophagy

Wang

Zou

et al. 2018

Bioscience Reports

View full text Add to dashboard Cite

AMP-activated protein kinase (AMPK), a serine/threonine protein kinase, has been shown to exert a protective effect against cardiac hypertrophy and heart failure. Our previous reports have demonstrated that AMPK can inhibit cardiac hypertrophy and block the development of heart failure by promoting autophagy. However, other investigators have demonstrated that overactive and dysregulated autophagy may also contribute to the onset and exacerbation of heart failure. Thus, a major goal of the present investigation is to explore how AMPK regulates autophagy in heart failure. First, heart failure was induced in mice by 4 weeks of pressure overload; AMPK activation was subsequently induced by injecting 5-aminoimidazole-4-carboxamide 1-β-d-ribonucleotide (AICAR) after the establishment of chronic heart failure. We showed that AMPK activation significantly attenuated the progression of heart failure and improved cardiac function, which was accompanied by decreased autophagy levels in the failing hearts. Additionally, we demonstrated that the treatment with AICAR inhibited phosphorylation of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) downstream effectors 4E-binding protein1 (4EBP1), and ribosomal protein S6 kinase (p70S6K). A major action of AICAR was significantly to activate AKT (Ser473), the downstream substrate of mTOR complex 2 (mTORC2). In conclusion, the data suggest that AMPK improved cardiac function during the development of chronic heart failure by attenuating autophagy, potentially via mTORC2 activation and the downstream effects.

show abstract

AMPK in Cardiovascular Diseases

Cited by 28 publications

References 132 publications

Spermidine‐enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway

Spermidine‐enhanced autophagic flux improves cardiac dysfunction following myocardial infarction by targeting the AMPK/mTOR signalling pathway

Deconvoluting AMP-activated protein kinase (AMPK) adenine nucleotide binding and sensing

AMPK blunts chronic heart failure by inhibiting autophagy

Contact Info

Product

Resources

About