AMPK in cardiac fibrosis and repair: Actions beyond metabolic regulation

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

doi:10.1016/j.yjmcc.2016.01.001

Cited by 108 publications

(80 citation statements)

References 192 publications

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“…4 Recent studies have found that AMPK was involved in the development of cancer, cardiac fibrosis, Huntington's disease and so on. 26, 27, 28 In the present study, we found that AMPK was activated in mice with LPS/D-Gal-induced fulminant hepatitis. Pharmacological inhibition of AMPK by compound C significantly suppressed the elevation of plasma aminotransferases, alleviated the histological alterations and increased the survival rate of experimental animals.…”

Section: Discussionsupporting

confidence: 55%

Endogenous AMPK acts as a detrimental factor in fulminant hepatitis via potentiating JNK-dependent hepatocyte apoptosis

Gong

et al. 2017

Cell Death Dis

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The energy sensor AMP-activated protein kinase (AMPK) is crucial for energy homeostasis. Recent studies have revealed that AMPK is involved in various energy-intensive pathological processes such as inflammation and apoptosis. The physiological functions of hepatic AMPK have been well studied, but the pathological significance of AMPK in liver disorders remains largely unknown. In the present study, the phosphorylation status and the roles of AMPK were investigated in mice with lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced fulminant hepatitis. The experimental data indicated that the phosphorylation of hepatic AMPK increased in mice with LPS/D-Gal-induced fulminant hepatitis. Pretreatment with the AMPK inhibitor compound C enhanced the early production of pro-inflammatory cytokines but suppressed the late activation of the caspase cascade, reduced the number of TUNEL-positive cells, decreased the elevation of aminotransferases, alleviated the histological abnormalities and improved the survival rate of LPS/D-Gal-insulted mice. Pretreatment with compound C suppressed LPS/D-Gal-induced phosphorylation of JNK. Inhibition of JNK alleviated LPS/D-Gal-induced liver injury, but the level of p53 remained unchanged in mice exposed to LPS/D-Gal. Post-insult treatment with the AMPK activator A-769662 further increased the phosphorylation levels of AMPK and JNK, enhanced hepatocyte apoptosis and deteriorated liver injury, all of these effects could be reversed by co-administration of the AMPK inhibitor or JNK inhibitor. Interestingly, post-insult treatment with the AMPK inhibitor also resulted in beneficial outcomes. These data suggested that AMPK might be a late detrimental factor in LPS/D-Gal-induced hepatitis via potentiating JNK-dependent hepatocyte apoptosis and AMPK might become a pharmacological target for the intervention of fulminant hepatitis.

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Section: Discussionsupporting

confidence: 55%

Endogenous AMPK acts as a detrimental factor in fulminant hepatitis via potentiating JNK-dependent hepatocyte apoptosis

Gong

et al. 2017

Cell Death Dis

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“…However, it has recently been demonstrated in liver that this protein mediates in the activation of AMPK, a ubiquitously-expressed cellular energy sensor [22]. In heart, AMPK appears to possess an essential role in regulating fibrosis of the myocardium since its activation inhibits mTOR expression and therefore cell growth [21]. However, despite the fact that in this study AMPKt increases after fructose exposure in pups, its activation is significantly reduced as shown by the p-AMPK/AMPKt ratio.…”

Section: Discussioncontrasting

confidence: 52%

Heart selenoproteins status of metabolic syndrome-exposed pups: A potential target for attenuating cardiac damage

Serrano

Nogales

Sánchez-Sobrino

et al. 2016

Mol. Nutr. Food Res.

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“…Metformin reduces ROS generation and ameliorates oxidative stress-induced apoptosis and inflammation in cardiomyocytes [108] and endothelial cells [109]. It also protects against I/R-induced myocardial fibrosis by inhibiting fibrotic factors, including TGF- β 1, TNF- α and basic fibroblast growth factor (bFGF) in the circulation and the myocardium [110, 111]. As a routine oral agent for T2DM, metformin might be a potential pharmacological therapeutic target to protect against MI/R injury under diabetes on the regulation of cardiac oxidative stress and mTOR signaling.…”

Section: Potential Cardiometabolic Target Against Diabetic Mi/r Inmentioning

confidence: 99%

Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes

Zhao

Yang

2017

Oxidative Medicine and Cellular Longevity

146

124

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Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress. mTOR signaling presents both cardioprotective and cardiotoxic effects on the diabetic heart, which interplays with oxidative stress directly or indirectly. Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets. In this review, we will focus on the role of oxidative stress and mTOR signaling in the pathophysiology of MI/R injury in diabetes and discuss potential mechanisms and their interactions in an effort to provide some evidence for cardiometabolic targeted therapies for ischemic heart disease (IHD).

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AMPK in cardiac fibrosis and repair: Actions beyond metabolic regulation

Cited by 108 publications

References 192 publications

Endogenous AMPK acts as a detrimental factor in fulminant hepatitis via potentiating JNK-dependent hepatocyte apoptosis

Endogenous AMPK acts as a detrimental factor in fulminant hepatitis via potentiating JNK-dependent hepatocyte apoptosis

Heart selenoproteins status of metabolic syndrome-exposed pups: A potential target for attenuating cardiac damage

Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes

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