The ubiquitin E3 ligase TRAF6 exacerbates pathological cardiac hypertrophy via TAK1-dependent signalling

Ji, Yan‐Xiao; Zhang, Peng; Zhang, Xiaojing; Zhao, Yichao; Deng, Ke‐Qiong; Jiang, Xi; Wang, Pi-Xiao; Huang, Zan; Li, Hongliang

doi:10.1038/ncomms11267

Cited by 148 publications

(121 citation statements)

References 70 publications

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“…Adult (8–10 week old) male mice (body weights of 24–27 g) were subjected to AB or a sham operation as previously described 20, 21. Briefly, the mice were anesthetized via an intraperitoneal injection of sodium pentobarbital (50 mg/kg, Sigma‐Aldrich),the left chest of each mouse was opened to identify the thoracic aorta by blunting dissection at the second intercostal space.…”

Section: Methodsmentioning

confidence: 99%

ADAM23 in Cardiomyocyte Inhibits Cardiac Hypertrophy by Targeting FAK‐AKT Signaling

Xiang

Luo

et al. 2018

JAHA

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BackgroundCardiac hypertrophy has been recognized as an important independent risk factor for the development of heart failure and increases the risk of cardiac morbidity and mortality. A disintegrin and metalloprotease 23 (ADAM23), a member of ADAM family, is involved in cancer and neuronal differentiation. Although ADAM23 is expressed in the heart, the role of ADAM23 in the heart and in cardiac diseases remains unknown.Methods and ResultsWe observed that ADAM23 expression is decreased in both failing human hearts and hypertrophic mice hearts. Cardiac‐specific conditional ADAM23‐knockout mice significantly exhibited exacerbated cardiac hypertrophy, fibrosis, and dysfunction, whereas transgenic mice overexpressing ADAM23 in the heart exhibited reduced cardiac hypertrophy in response to pressure overload. Consistent results were also observed in angiotensin II‐induced neonatal rat cardiomyocyte hypertrophy. Mechanistically, ADAM23 exerts anti‐hypertrophic effects by specifically targeting the focal adhesion kinase‐protein kinase B (FAK‐AKT) signaling cascade. Focal adhesion kinase inactivation by inhibitor (PF‐562271) greatly reversed the detrimental effects in ADAM23‐knockout mice subjected to aortic banding.ConclusionAltogether, we identified ADAM23 as a negative regulator of cardiac hypertrophy through inhibiting focal adhesion kinase‐protein kinase B signaling pathway, which could be a promising therapeutic target for this malady.

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Section: Methodsmentioning

confidence: 99%

ADAM23 in Cardiomyocyte Inhibits Cardiac Hypertrophy by Targeting FAK‐AKT Signaling

Xiang

Luo

et al. 2018

JAHA

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“…Adequate anesthesia was confirmed by the absence of a toe pinch reflex. The procedure was performed according to Ji et al [17]. We use temgesic (0.1mg·kg -1 ) once daily for 6 days post-surgery to treat post-operative pain.…”

Section: Methodsmentioning

confidence: 99%

“…Protein extract and Western blotting were performed essentially as described previously [17]. Protein expression levels were normalized to the matched total proteins or GAPDH.…”

Section: Methodsmentioning

confidence: 99%

Sesamin Protects Against Cardiac Remodeling Via Sirt3/ROS Pathway

Fan

Zheng

Liu

et al. 2017

Cell Physiol Biochem

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Background/Aims: Cardiac remodeling is associated with oxidative stress. Sesamin, a well-known antioxidant from sesamin seeds, have been used extensively as traditional health foods. However, there is little known about the effect of sesamin on cardiac remodeling. Therefore, the present study aimed to determine whether sesamin could protect against cardiac remodeling and to clarify potential molecular mechanisms. Methods: The mice were subjected to either transverse aortic constriction (TAC) or sham surgery (control group). Beginning one week after surgery, the mice were oral gavage treated with sesamin (100mg·kg^-1·day^-1) or vehicle for 3 weeks. Cardiac hypertrophy was assessed by echocardiographic parameters, histological analyses and hypertrophic markers. Results: Sesamin alleviated cardiac hypertrophy, inhibited fibrosis and attenuated the inflammatory response. The increased production of reactive oxygen species, the activation of ERK1/2-dependent nuclear factor-κB and the increased level of Smad2 phosphorylation were observed in cardiac remolding model that were treated with sesamin. Furthermore, TAC induced alteration of Sirt3 and SOD2 was normalized by sesamin treatment. Finally, a selective Sirt3 inhibitor 3-TYP blocks all the protective role of sesamin, suggesting that a Sirt3-dependent effect of sesamin on cardiac remodeling. Conclusion: Sesamin improves cardiac function and prevents the development of cardiac hypertrophy via Sirt3/ROS pathway. Our results suggest the protective effect of sesamin on cardiac remolding.

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“…It is well defined that the expression of TRAF6 and the activity of TAK1‐JNK1/2/p38 cascade are increased in failing human heart. Thus, NADPH oxidase‐dependent accumulation of ROS triggers TRAF6 auto‐ubiquitination and subsequent K63‐linked ubiquitination and phosphorylation of TAK1 triggering downstream cascade of pathological hypertrophy 65, 66 (Figure 2). Together, these reports indicate that ubiquitination machineries have diverse role in cellular function and disease development, in particular, in cardiovascular system.…”

Section: K63‐ubiquitination Plays An Important Role In Nf‐κb Activatimentioning

confidence: 99%

The role of K63‐linked polyubiquitination in cardiac hypertrophy

Ponnusamy

Xin

et al. 2018

J Cellular Molecular Medi

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Ubiquitination, also known as ubiquitylation, is a vital post‐translational modification of proteins that play a crucial role in the multiple biological processes including cell growth, proliferation and apoptosis. K63‐linked ubiquitination is one of the vital post‐translational modifications of proteins that are involved in the activation of protein kinases and protein trafficking during cell survival and proliferation. It also contributes to the development of various disorders including cancer, neurodegeneration and cardiac hypertrophy. In this review, we summarize the role of K63‐linked ubiquitination signalling in protein kinase activation and its implications in cardiac hypertrophy. We have also provided our perspectives on therapeutically targeting K63‐linked ubiquitination in downstream effector molecules of growth factor receptors for the treatment of cardiac hypertrophy.

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The ubiquitin E3 ligase TRAF6 exacerbates pathological cardiac hypertrophy via TAK1-dependent signalling

Cited by 148 publications

References 70 publications

ADAM23 in Cardiomyocyte Inhibits Cardiac Hypertrophy by Targeting FAK‐AKT Signaling

ADAM23 in Cardiomyocyte Inhibits Cardiac Hypertrophy by Targeting FAK‐AKT Signaling

Sesamin Protects Against Cardiac Remodeling Via Sirt3/ROS Pathway

The role of K63‐linked polyubiquitination in cardiac hypertrophy

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