Peroxisome proliferator–activated receptor gamma coactivator 1 alpha protects cardiomyocytes from hypertrophy by suppressing calcineurin-nuclear factor of activated T cells c4 signaling pathway

Liu, Xueping; Gao, Hui; Huang, Xiaoyang; Chen, Yanfang; Feng, Xiaohai; He, Yihua; Li, Zhuo-ming; Liu, Peiqing

doi:10.1016/j.trsl.2015.06.003

Cited by 19 publications

(18 citation statements)

References 45 publications

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“…The pathological hypertrophic development involves multiple intracellular signaling pathways, including the enhancement of calcium‐regulated signaling pathways (Bernardo et al, 2010). Among them, calcineurin/nuclear factor of activated T‐cell (NFAT) pathway plays a key role in pathological cardiac hypertrophy (Liu et al, 2015; Nakayama et al, 2013; Sarikhani et al, 2018). Calcineurin is a cytoplasmic calcium‐/calmodulin‐activated phosphatase that regulates hypertrophy response (Dierck et al, 2017; Martinez‐Martinez et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Zebrafish hhatla is involved in cardiac hypertrophy

Shi

Gong

Chen

et al. 2020

Journal Cellular Physiology

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Cardiac hypertrophy is a compensatory response to pathological stimuli, ultimately progresses to cardiomyopathy, heart failure, or sudden death. Although many signaling pathways have been reported to be involved in the hypertrophic process, it is still not fully clear about the underlying molecular mechanisms for cardiac hypertrophy. Hedgehog acyltransferase‐like (Hhatl), a sarcoplasmic reticulum‐resident protein, exhibits high expression in the heart and muscle. However, the biological role of Hhatl in the heart remains unknown. In this study, we first found that the expression level of Hhatl is markedly decreased in cardiac hypertrophy. We further studied the role of hhatla, homolog of Hhatl with the zebrafish model. The depletion of hhatla in zebrafish leads to cardiac defects, as well as an enhanced level of hypertrophic markers. Besides, we found that calcineurin signaling participates in hhatla depletion‐induced cardiac hypertrophy. Together, these results demonstrate a critical role for hhatla in cardiac hypertrophy.

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Section: Introductionmentioning

confidence: 99%

Zebrafish hhatla is involved in cardiac hypertrophy

Shi

Gong

Chen

et al. 2020

Journal Cellular Physiology

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“…Phenylephrine has been widely utilized as a stimulus of cardiac hypertrophy (Liu et al ., ). Cultures of NRCMs were incubated with 100 μM phenylephrine for the times indicated.…”

Section: Resultsmentioning

confidence: 97%

Sirtuin 1 represses PKC‐ζ activity through regulating interplay of acetylation and phosphorylation in cardiac hypertrophy

Huang

Lü

et al. 2018

British J Pharmacology

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Background and Purpose Activation of PKC‐ζ is closely linked to the pathogenesis of cardiac hypertrophy. PKC‐ζ can be activated by certain lipid metabolites such as phosphatidylinositol (3,4,5)‐trisphosphate and ceramide. However, its endogenous negative regulators are not well defined. Here, the role of the sirtuin1‐PKC‐ζ signalling axis and the underlying molecular mechanisms were investigated in cardiac hypertrophy. Experimental Approach Cellular hypertrophy in cultures of cardiac myocytes, from neonatal Sprague‐Dawley rats, was monitored by measuring cell surface area and the mRNA levels of hypertrophic biomarkers. Interaction between sirtuin1 and PKC‐ζ was investigated by co‐immunoprecipitation and confocal immunofluorescence microscopy. Sirtuin1 activation was enhanced by resveratrol treatment or Ad‐sirtuin1 transfection. A model of cardiac hypertrophy in Sprague‐Dawley rats was established by abdominal aortic constriction surgery or induced by isoprenaline in vivo. Key Results Overexpression of PKC‐ζ led to cardiac hypertrophy and increased activity of NF‐κB, ERK1/2 and ERK5, which was ameliorated by sirtuin1 overexpression. Enhancement of sirtuin1 activity suppressed acetylation of PKC‐ζ, hindered its binding to phosphoinositide‐dependent kinase 1 and inhibited PKC‐ζ phosphorylation in cardiac hypertrophy. Consequently, the downstream pathways of PKC‐ζ' were suppressed in cardiac hypertrophy. This regulation loop suggests a new role for sirtuin1 in mediation of cardiac hypertrophy. Conclusions and Implications Sirtuin1 is an endogenous negative regulator for PKC‐ζ and mediates its activity via regulating the acetylation and phosphorylation in the pathogenesis of cardiac hypertrophy. Targeting the sirtuin1‐PKC‐ζ signalling axis may suggest a novel therapeutic approach against cardiac hypertrophy.

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“…The expression of PGC-1α and its targets is downregulated in pathological cardiac hypertrophy and failing heart (Finck and Kelly, 2007 ). However, moderate overexpression of PGC-1α contributes to the protective effect of cardiomyocytes (Rowe et al, 2010 ; Liu et al, 2015 ), which could be elucidated by the regulation of the glucose uptake and oxidation (Finck and Kelly, 2006 ). Our study showed that CIHH increased the expression of PGC-1α both mRNA and protein, suggesting PGC-1α could improve the glucose uptake and oxidation, which may improve the energy metabolism of the cardiomyocytes and reduce the I/R injury in rat heart.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Glucose Metabolism via PGC-1α Participates in the Cardioprotection of Chronic Intermittent Hypobaric Hypoxia

Liu

et al. 2016

Front. Physiol.

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Background and Aims: Previous studies demonstrated that energy metabolism disturbance impairs cardiac function and chronic intermittent hypobaric hypoxia (CIHH) protects heart against ischemia/reperfusion injury. The present study aimed to test the hypothesis that CIHH protects the heart against ischemia/reperfusion (I/R) injury via improvement of cardiac glucose metabolism.Methods: Male Sprague-Dawley rats received CIHH treatment simulating 5000-m altitude for 28 days, 6 h per day in a hypobaric chamber or no treatment (control). Body weight, fasting blood glucose, blood lipid and glucose tolerance were measured. The left ventricular function of isolated hearts was evaluated during 30 min of ischemia and 60 min of reperfusion using Langendorff method. The mRNA and protein expression involved in cardiac energy metabolism was determined using quantitative PCR and Western blot techniques.Results: 1. There was no difference of body weight, fast blood glucose, blood lipid and glucose tolerance between control and CIHH rats under baseline condition (p > 0.05). 2. The recovery of left ventricular function after I/R was improved significantly in CIHH rats compared to control rats (p < 0.05). 3. The expression of cardiac GLUT4 and PGC-1α was increased but PDK4 gene expression was decreased by CIHH treatment at both mRNA and protein level. Also p-AMPK/AMPK ratio was increased in CIHH rats (p < 0.05).Conclusion: CIHH ameliorates I/R injury through improving cardiac glucose metabolism via upregulation of GLUT4, p-AMPK, and PGC-1α expressions, but downregulation of cardiacPDK4 expression.

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Peroxisome proliferator–activated receptor gamma coactivator 1 alpha protects cardiomyocytes from hypertrophy by suppressing calcineurin-nuclear factor of activated T cells c4 signaling pathway

Cited by 19 publications

References 45 publications

Zebrafish hhatla is involved in cardiac hypertrophy

Zebrafish hhatla is involved in cardiac hypertrophy

Sirtuin 1 represses PKC‐ζ activity through regulating interplay of acetylation and phosphorylation in cardiac hypertrophy

Enhancement of Glucose Metabolism via PGC-1α Participates in the Cardioprotection of Chronic Intermittent Hypobaric Hypoxia

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