Adenosine monophosphate-activated protein kinase inhibits cardiac hypertrophy through reactivating peroxisome proliferator-activated receptor-α signaling pathway

Wang, Mengqi; Pei, Zhaohui; Yin, Ran; Zhang, Cheng-Xi; Chen, Baolin; Zhang, Yang; Liú, Dan; Xu, Anlong; Dong, Yugang

doi:10.1016/j.ejphar.2009.08.024

Cited by 46 publications

(39 citation statements)

References 27 publications

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“…Previous studies have suggested that AMPK activation inhibits the development of cardiac hypertrophy [24,25] . Consistent with these fi ndings, our results here show that activation of AMPK by AICAR significantly suppresses cardiomyocyte hypertrophy as evidenced by decreased cardiomyocyte area, reduced expression of the hypertrophy-associated gene β-MHC, and enhanced protein degradation in PE-stimulated cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Neonatal cardiomyocytes were prepared as described previously [25] . Briefly, ventricles from one-to three-day-old neonatal SD rats were cut into pieces of approximately 1 mm and treated with 0.125% trypsin and 0.05% collagenase type I.…”

Section: Drugs and Chemicalsmentioning

confidence: 99%

“…However, the role of AMPK activation on atrophy-related signals in cardiomyocytes has not been established. Recent studies have shown that AMPK activation might inhibit the development of cardiac hypertrophy [24][25][26] . However, it is unclear whether the cardioprotective effects of AMPK for cardiac hypertrophy are mediated by the FOXO1/ MuRF1 pathway.…”

Section: Wwwchinapharcom Chen Bl Et Almentioning

confidence: 99%

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Activation of AMPK inhibits cardiomyocyte hypertrophy by modulating of the FOXO1/MuRF1 signaling pathway in vitro

Chen

Wang

et al. 2010

Acta Pharmacol Sin

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Aim: To examine the inhibitory effects of adenosine monophosphate-activated protein kinase (AMPK) activation on cardiac hypertrophy in vitro and to investigate the underlying molecular mechanisms. Methods: Cultured neonatal rat cardiomyocytes were treated with the specifi c AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the specifi c AMPK antagonist Compound C, and then stimulated with phenylephrine (PE). The Muscle RING fi nger 1 (MuRF1)-small interfering RNA (siRNA) was transfected into cardiomyocytes using Lipofectamine 2000. The surface area of cultured cardiomyocytes was measured using planimetry. The protein degradation was determined using high performance liquid chromatography (HPLC). The expression of β-myosin heavy chain (β-MHC) and MuRF1, as well as the phosphorylation levels of AMPK and Forkhead box O 1 (FOXO1), were separately measured using Western blot or real-time polymerase chain reaction. Results: Activation of AMPK by AICAR 0.5 mmol/L inhibited PE-induced increase in cardiomyocyte area and β-MHC protein expression and PE-induced decrease in protein degradation. Furthermore, AMPK activation increased the activity of transcription factor FOXO1 and up-regulated downstream atrogene MuRF1 mRNA and protein expression. Treatment of hypertrophied cardiomyocytes with Compound C 1 μmol/L blunted the effects of AMPK on cardiomyocyte hypertrophy and changes to the FOXO1/MuRF1 pathway. The effects of AICAR on cardiomyocyte hypertrophy were also blocked after MuRF1 was silenced by transfection of cardiomyocytes with MuRF1-siRNA. Conclusion: The present study demonstrates that AMPK activation attenuates cardiomyocyte hypertrophy by modulating the atrophyrelated FOXO1/MuRF1 signaling pathway in vitro.

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Section: Discussionmentioning

confidence: 99%

Section: Drugs and Chemicalsmentioning

confidence: 99%

Section: Wwwchinapharcom Chen Bl Et Almentioning

confidence: 99%

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Activation of AMPK inhibits cardiomyocyte hypertrophy by modulating of the FOXO1/MuRF1 signaling pathway in vitro

Chen

Wang

et al. 2010

Acta Pharmacol Sin

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“…It has been known that activation of AMPK prevents aortic banding-induced cardiac hypertrophy 40 by enhancement of peroxisome proliferator-activated receptor-α signaling in the heart 31 and that AMPK induces SHP in response to metformin in hepatocytes. 27 In the present study, we also observed that metformin activates AMPK in cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

Small Heterodimer Partner Blocks Cardiac Hypertrophy by Interfering With GATA6 Signaling

Nam

Kim

Joung

et al. 2014

Circulation Research

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Cardiac hypertrophy is an increase in the individual cellular volume of the heart and is an adaptive response to exogenous stresses. The increase in cellular volume is associated with reactivation of the fetal gene program, which is finely regulated by diverse cardiac transcription factors.1 Specifically, GATA4, GATA6, myocyte enhancer factor 2C, nuclear factor of activated T cells, NK2 homeobox 5, and serum response factor have been shown to be involved in the development of cardiac hypertrophy.1 GATA4 and GATA6 are heart-specific transcription factors that regulate pathological cardiac hypertrophy in association with atrial natriuretic factor (ANF) expression.2,3 Transgenic mice that overexpress GATA4 in the heart show cardiac hypertrophy, 4 and GATA4 activity is regulated by physical interaction with other transcription factors, such as serum response factor, NK2 homeobox 5, and myocyte enhancer factor 2.5-7 GATA6 also induces pathological cardiac hypertrophy, which was demonstrated by recent studies of cardiac-specific overexpression of GATA6 in mice. 3In addition to effects as transcription factors, some of these factors also act as nuclear receptors that provide signal-mediated responsiveness to endogenous or exogenous ligands. For example, peroxisome proliferator-activated receptor-α or steroid receptors respond to a ligand and then mediate diverse cellular events as well as metabolic regulation.8,9 Not surprisingly, these nuclear receptors also play important roles in various organs, and therapeutic applications of their modulators are growing. The nuclear receptors are classified depending on their structural similarities. Interestingly, 1 group of nuclear receptors is termed the orphan nuclear receptors. In contrast with the other nuclear receptors that have endogenous ligands

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“…Estudos in vivo também mostraram que a ativação farmacológica da AMPK foi capaz de amenizar a hipertrofia cardíaca de ratos que foram submetidos à constrição transaórtica (TAC) (MENG et al, 2009). …”

Section: Efeitos Da Ativação E Inibição Da Ampk Na Hipertrofia Do Carunclassified

Análise do papel da proteína quinase ativada pela AMP (AMPK) na hipertrofia do cardiomiócito induzida pelo hormônio tiroideano.

Takano¹

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Previous studies of literature, including our laboratory results have shown that high levels of thyroid hormones (TH) induce significant cardiac hypertrophy, observed both in vivo and in vitro experiments. Recently, some studies have shown that TH are also able to rapidly modulate the phosphorylation state of protein kinases related to cardiac hypertrophy process by non-genomic actions. In this sense, experimental evidences indicate that AMP-activated protein kinase (AMPK) is an important target in the control of hypertrophic growth, since the activation of this enzyme determines wide variety of physiological effects, including the control of enzymes related to protein synthesis. Thus, the objectives of this study were to evaluate the effects of TH on the modulation of AMPK signaling pathway and to check the possible involvement of this kinase in vitro model of hypertrophy induced by TH. The results showed that this hormone rapidly activates AMPK and related proteins to this signaling. Furthermore, pharmacological stimulation of AMPK attenuated cardiomyocyte hypertrophy induced by TH. These data suggest that AMPK is a possible and interesting therapeutic tool in cardiovascular disease such as cardiac hypertrophy.

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Adenosine monophosphate-activated protein kinase inhibits cardiac hypertrophy through reactivating peroxisome proliferator-activated receptor-α signaling pathway

Cited by 46 publications

References 27 publications

Activation of AMPK inhibits cardiomyocyte hypertrophy by modulating of the FOXO1/MuRF1 signaling pathway in vitro

Activation of AMPK inhibits cardiomyocyte hypertrophy by modulating of the FOXO1/MuRF1 signaling pathway in vitro

Small Heterodimer Partner Blocks Cardiac Hypertrophy by Interfering With GATA6 Signaling

Análise do papel da proteína quinase ativada pela AMP (AMPK) na hipertrofia do cardiomiócito induzida pelo hormônio tiroideano.

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