Exogenous GDF11 attenuates non-canonical TGF-β signaling to protect the heart from acute myocardial ischemia–reperfusion injury

Su, Hsing-Hui; Liao, Jiuan-Miaw; Wang, Yi-Hsin; Chen, Kemin; Lin, Ching-Yi; Lee, I‐Hui; Li, Yi-Ju; Huang, Jing‐Yang; Tsai, Shen Kou; Yen, Jiin Cherng; Huang, Shiang‐Suo

doi:10.1007/s00395-019-0728-z

Cited by 54 publications

(47 citation statements)

References 49 publications

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“…Genetic ablation of Mst2 attenuates inflammation-related hepatic injury ( Kim et al, 2018 ). In cardiac diseases, cardiomyocyte dysfunction is related to inflammation that affects mitochondrial homeostasis ( Silverblatt et al, 2019 ; Su et al, 2019 ). In this study, we aimed to understand the mechanistic role of Mst2 in inflammation-induced cardiomyocyte dysfunction using H9C2 cardiomyocytes as a model.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission

Tian

Song²,

Qin

et al. 2020

Front. Physiol.

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In this study, we analyzed the role of mammalian STE20-like protein kinase 2 (Mst2), a serine-threonine protein kinase, in Lipopolysaccharides (LPS)-mediated inflammation and apoptosis in the H9C2 cardiomyocytes. Mst2 mRNA and protein levels were significantly upregulated in the LPS-treated H9C2 cardiomyocytes. LPS treatment induced expression of IL-2, IL-8, and MMP9 mRNA and proteins in the H9C2 cardiomyocytes, and this was accompanied by increased caspase-3/9 mediating H9C2 cardiomyocyte apoptosis. LPS treatment also increased mitochondrial reactive oxygen species (ROS) and the levels of antioxidant enzymes, such as GSH, SOD, and GPX, in the H9C2 cardiomyocytes. The LPS-treated H9C2 cardiomyocytes showed lower cellular ATP levels and mitochondrial state-3/4 respiration but increased mitochondrial fragmentation, including upregulation of the mitochondrial fission genes Drp1, Mff, and Fis1. LPS-induced inflammation, mitochondrial ROS, mitochondrial fission, and apoptosis were all significantly suppressed by pre-treating the H9C2 cardiomyocytes with the Mst2 inhibitor, XMU-MP1. However, the beneficial effects of Mst2 inhibition by XMU-MP1 were abolished by carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP), a potent activator of mitochondrial fission. These findings demonstrate that Mst2 mediates LPS-induced cardiomyocyte inflammation and apoptosis by increasing mitochondrial fission.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission

Tian

Song²,

Qin

et al. 2020

Front. Physiol.

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“…One of the factors identified in parabiosis experiments was GDF11, which was shown to rejuvenate the aged brain (Katsimpardi et al, ), while having a broader rejuvenating effect on other peripheral aged organs, such as the muscle and heart (Loffredo et al, ; Sinha et al, ). Subsequently, other reports argued that GDF11 was positively associated with aging, cachexia, and inhibition of muscle regeneration in aged mice (Egerman et al, ; Harper et al, ; Jones et al, ), while different studies showed a beneficial role for GDF11 in the periphery (Poggioli et al, ; Su et al, ; Walker et al, ). In the central nervous system, GDF11 was also shown to be neuroprotective for neurovascular recovery and neurogenesis (Anqi, Ruiqi, Yanming, & Chao, ; Ma et al, ; Ozek, Krolewski, Buchanan, & Rubin, ; Schafer & LeBrasseur, ; Zhang et al, ).…”

Section: Introductionmentioning

confidence: 99%

Systemic GDF11 stimulates the secretion of adiponectin and induces a calorie restriction‐like phenotype in aged mice

et al. 2019

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Aging is a negative regulator of general homeostasis, tissue function, and regeneration. Changes in organismal energy levels and physiology, through systemic manipulations such as calorie restriction and young blood infusion, can regenerate tissue activity and increase lifespan in aged mice. However, whether these two systemic manipulations could be linked has never been investigated. Here, we report that systemic GDF11 triggers a calorie restriction-like phenotype without affecting appetite or GDF15 levels in the blood, restores the insulin/IGF-1 signaling pathway, and stimulates adiponectin secretion from white adipose tissue by direct action on adipocytes, while repairing neurogenesis in the aged brain. These findings suggest that GDF11 has a pleiotropic effect on an organismal level and that it could be a linking mechanism of rejuvenation between heterochronic parabiosis and calorie restriction. As such, GDF11 could be considered as an important therapeutic candidate for age-related neurodegenerative and metabolic disorders. K E Y W O R D Sadiponectin, aging, calorie restriction, GDF11, heterochronic parabiosis, rejuvenation | 9 of 11 KATSIMPARDI eT Al. GDF11 (Peprotech, was dissolved in water, further diluted according to the manufacturer's instructions, and injected at a concentration of 1 mg/kg. Control mice (young or aged) were injected with equivalent volumes of saline. Injection concentration was chosen based on a pilot study with three different concentrations (0.1, 0.5, and 1.0 mg/kg) where consistent weight loss and brain rejuvenation were observed upon 1 mg/kg GDF11 administration. The half-life of GDF11 at these concentrations was found to be of 12 hr. | GDF11 administration

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“…In addition, LDL is primarily degraded by endothelium through the LDL receptor, which is expressed on the surface of endothelium. Impaired endothelial function is associated with an increase in the blood LDL ( Su et al, 2019 ). Based on this information, endothelium is an ideal barrier to regulate hyperlipemia.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction

Tan

et al. 2020

Front. Cell Dev. Biol.

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Statin treatment reduces cardiovascular risk. However, individuals with well-controlled low-density lipoprotein (LDL) levels may remain at increased risk owing to persistent high triglycerides and low high-density lipoprotein cholesterol. Because resveratrol promotes glucose metabolism and mitigates cardiovascular disorders, we explored its mechanism of protective action on high-fat-induced endothelial dysfunction. Human umbilical venous endothelial cells were treated with oxidized LDL (ox-LDL) in vitro. Endothelial function, cell survival, proliferation, migration, and oxidative stress were analyzed through western blots, quantitative polymerase chain reaction, ELISA, and immunofluorescence. ox-LDL induced endothelial cell apoptosis, proliferation arrest, and mobilization inhibition, all of which resveratrol reduced. ox-LDL suppressed the activities of mitochondrial respiration complex I and III and reduced levels of intracellular antioxidative enzymes, resulting in reactive oxygen species overproduction and mitochondrial dysfunction. Resveratrol treatment upregulated Bnip3-related mitophagy and prevented ox-LDL-mediated mitochondrial respiration complexes inactivation, sustaining mitochondrial membrane potential and favoring endothelial cell survival. We found that resveratrol enhanced Bnip3 transcription through hypoxia-inducible factor 1 (HIF1) and 5 AMP-activated protein kinase (AMPK). Inhibition of AMPK and HIF1 abolished resveratrol-mediated protection of mitochondrial redox balance and endothelial viability. Together, these data demonstrate resveratrol reduces hyperlipemiarelated endothelial damage by preserving mitochondrial homeostasis.

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Exogenous GDF11 attenuates non-canonical TGF-β signaling to protect the heart from acute myocardial ischemia–reperfusion injury

Cited by 54 publications

References 49 publications

RETRACTED: Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission

RETRACTED: Mammalian STE20-Like Kinase 2 Promotes Lipopolysaccharides-Mediated Cardiomyocyte Inflammation and Apoptosis by Enhancing Mitochondrial Fission

Systemic GDF11 stimulates the secretion of adiponectin and induces a calorie restriction‐like phenotype in aged mice

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction

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