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

Chen, Baolin; Ma, Yuedong; Wang, Mengqi; Xiong, Zhaojun; Wang, Haining; Zeng, Junyi; Liu, Chen; Dong, Yugang

doi:10.1038/aps.2010.73

Cited by 42 publications

(23 citation statements)

References 36 publications

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“…Sustained Akt activation induces cardiac hypertrophy, which may be through its regulation on mTOR pathway. AMP-activated protein kinase (AMPK) induces autophagy through its downstream target phosphorylation of mTOR 33, which might be one of the mechanisms of the favorable effects of AMPK in inhibiting cardiac hypertrophy 34.…”

Section: Discussionmentioning

confidence: 99%

PKD knockdown inhibits pressure overload-induced cardiac hypertrophy by promoting autophagy via AKT/mTOR pathway

Zhao

Wang

et al. 2017

Int. J. Biol. Sci.

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Growing evidence shows that protein kinase D (PKD) plays an important role in the development of pressure overload-induced cardiac hypertrophy. However, the mechanisms involved are not clear. This study tested our hypothesis that PKD might mediate cardiac hypertrophy by negatively regulating autophagy using the technique of PKD knockdown by siRNA. Cardiac hypertrophy was induced in 8-week old male C57BL/6 mice by transverse aortic constriction (TAC). TAC mice were then divided into five groups receiving the treatments of vehicle (DMSO), an autophagy inducer rapamycin (1 mg/kg/day, i.p.), control siRNA, lentiviral PKD siRNA (2×108 transducing units/0.1 ml, i.v. injection in one day after surgery, and repeated in 2 weeks after surgery), and PKD siRNA plus 3-methyladenine (3-MA, an autophagy inhibitor, 20 mg/kg/day, i.p.), respectively. Four weeks after TAC surgery, echocardiographic study, hematoxylin and eosin (HE) staining, and Masson's staining showed mice with TAC had significantly hypertrophy and remodeling compared with sham animals. Treatments with PKD siRNA or rapamycin significantly ameliorated the cardiac hypertrophy and dysfunction. Moreover, PKD siRNA increased cardiac autophagic activity determined by electron micrographic study and the biomarkers by Western blot, accompanied with the downregulated AKT/mTOR/S6K signaling pathway. All the cardiac effects of PDK knockdown were inhibited by co-treatment with 3-MA. These results suggest that PKD is involved in the development of cardiac hypertrophy by inhibiting cardiac autophagy via AKT/mTOR pathway.

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Section: Discussionmentioning

confidence: 99%

PKD knockdown inhibits pressure overload-induced cardiac hypertrophy by promoting autophagy via AKT/mTOR pathway

Zhao

Wang

et al. 2017

Int. J. Biol. Sci.

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“…(Sin et al, 2014). Activation of AMPK inhibits cardiomyocyte hypertrophy by modulating the FOXO1/MuRF1 signaling pathway in vitro (Chen et al, 2010). Moreover, FOXO1 is the most well-recognized member of the FOXO family, functioning as a key mediator of autophagy (Zhang et al, 2015;Liu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

FOXO1 silence aggravates oxidative stress-promoted apoptosis in cardiomyocytes by reducing autophagy

Ning

Qiu

2015

J. Toxicol. Sci.

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-Mechanisms underlining oxidative stress-induced injury to cardiomyocytes during myocardial infarction (MI) or acute ischemia/reperfusion (I/R) are not well recognized. Forkhead box O (FOXO) transcription factors have been defined as critical mediators of oxidative stress resistance in multiple cell types, but their cardioprotective functions have not been reported previously. In the present study, we investigated the promotion to FOXO1 by the treatment with hydrogen peroxide (H 2 O 2 ) during the H 2 O 2 -induced apoptosis in cardiomyocyte H9c2 cells. We then silenced FOXO1 with FOXO1-specific siRNA, and re-evaluated the H 2 O 2 -induced apoptosis. In addition, we also examined the H 2 O 2 -induced autophagy and the autophagy induction post FOXO1 silence. Results demonstrated that H 2 O 2 induced a significantly high level of apoptosis in H9c2 cells. Interestingly, the FOXO1 in both mRNA and protein levels were not significantly regulated, however, the phosphorylated form of FOXO1 was significantly promoted in the H 2 O 2 -treated H9c2 cells. On the other hand, post the significant knockout of FOXO1 with the transfection with FOXO1-specific siRNA, the apoptosis induction was more significant in H9c2 cells subjected to H 2 O 2 . In addition, we found a significantly higher level of autophagy induction in the H 2 O 2 -treated H9c2 cells. However, the autophagy was markedly reduced by the knockout of FOXO1. In summary, these data support the critical role for FOXO1 in promoting cardiomyocytes against oxidative stress probably through inducing autophagy.

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“…In endothelial cells, adiponectin enhances eNOS activity and NO production via AMP‐activated protein kinase (AMPK)‐mediated phosphorylation of eNOS at Ser 1177 (Chen et al. 2003) and Ser 633 (Chen et al. 2009).…”

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confidence: 99%

Cross-talk between adipose tissue and vasculature: role of adiponectin

et al. 2010

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Adipose tissue is a highly dynamic endocrine organ, secreting a number of bioactive substances (adipokines) regulating insulin sensitivity, energy metabolism and vascular homeostasis. Dysfunctional adipose tissue is a key mediator that links obesity with insulin resistance, hypertension and cardiovascular disease. Obese adipose tissue is characterized by adipocyte hypertrophy and infiltration of inflammatory macrophages and lymphocytes, leading to the augmented production of pro-inflammatory adipokines and vasoconstrictors that induce endothelial dysfunction and vascular inflammation through their paracrine and endocrine actions. By contrast, the secretion of adiponectin, an adipokine with insulin sensitizing and anti-inflammatory activities, is decreased in obesity and its related pathologies. Emerging evidence suggests that adiponectin is protective against vascular dysfunction induced by obesity and diabetes, through its multiple favourable effects on glucose and lipid metabolism as well as on vascular function. Adiponectin improves insulin sensitivity and metabolic profiles, thus reducing the classical risk factors for cardiovascular disease. Furthermore, adiponectin protects the vasculature through its pleiotropic actions on endothelial cells, endothelial progenitor cells, smooth muscle cells and macrophages. Data from both animal and human investigations demonstrate that adiponectin is an important component of the adipo-vascular axis that mediates the cross-talk between adipose tissue and vasculature. This review highlights recent work on the vascular protective activities of adiponectin and discusses the molecular pathways underlying the vascular actions of this adipokine.

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

Cited by 42 publications

References 36 publications

PKD knockdown inhibits pressure overload-induced cardiac hypertrophy by promoting autophagy via AKT/mTOR pathway

PKD knockdown inhibits pressure overload-induced cardiac hypertrophy by promoting autophagy via AKT/mTOR pathway

FOXO1 silence aggravates oxidative stress-promoted apoptosis in cardiomyocytes by reducing autophagy

Cross-talk between adipose tissue and vasculature: role of adiponectin

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