Translating Translation to Mechanisms of Cardiac Hypertrophy

Zeitz, Μ.; Smyth, J. D.

doi:10.3390/jcdd7010009

Cited by 19 publications

(14 citation statements)

References 138 publications

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“…Nutritional effects, which can contribute to the development of some NCDs, can alter levels of growth factors, hormones, and cellular receptors that regulate signaling pathways that control both transcriptional and translational gene expression [10]. These alterations regulating translation initiation can directly control gene expression levels, with neurological, endocrine, pulmonary, and cardiovascular functions commonly disrupted [11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs)

Rios-Fuller

Mahé

Walters

et al. 2020

IJMS

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Non-communicable diseases (NCDs) are medical conditions that, by definition, are non-infectious and non-transmissible among people. Much of current NCDs are generally due to genetic, behavioral, and metabolic risk factors that often include excessive alcohol consumption, smoking, obesity, and untreated elevated blood pressure, and share many common signal transduction pathways. Alterations in cell and physiological signaling and transcriptional control pathways have been well studied in several human NCDs, but these same pathways also regulate expression and function of the protein synthetic machinery and mRNA translation which have been less well investigated. Alterations in expression of specific translation factors, and disruption of canonical mRNA translational regulation, both contribute to the pathology of many NCDs. The two most common pathological alterations that contribute to NCDs discussed in this review will be the regulation of eukaryotic initiation factor 2 (eIF2) by the integrated stress response (ISR) and the mammalian target of rapamycin complex 1 (mTORC1) pathways. Both pathways integrally connect mRNA translation activity to external and internal physiological stimuli. Here, we review the role of ISR control of eIF2 activity and mTORC1 control of cap-mediated mRNA translation in some common NCDs, including Alzheimer’s disease, Parkinson’s disease, stroke, diabetes mellitus, liver cirrhosis, chronic obstructive pulmonary disease (COPD), and cardiac diseases. Our goal is to provide insights that further the understanding as to the important role of translational regulation in the pathogenesis of these diseases.

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Section: Introductionmentioning

confidence: 99%

Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs)

Rios-Fuller

Mahé

Walters

et al. 2020

IJMS

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“…Lastly, while we identified a trend toward less protein translation in hearts from patients suffering from ischemic or dilated cardiomyopathy ( Figure 4 A) and in AC16 cells cultured in normoxia compared to physioxia ( Figure 5 A,C), very recent reports suggest that higher translation rates correlate with pressure overload and development of hypertrophy [ 62 , 63 ]. In the heart, the mammalian target of rapamycin complexes 1 and 2 (mTORC1 and 2) are the master regulators of cardiac translation-activating protein synthesis as a response to injury or pressure overload to enable adaptive hypertrophy [ 63 ], and hypertrophic signals were shown to activate mTORC and boost protein synthesis [ 64 ].…”

Section: Discussionmentioning

confidence: 71%

Mass Spectrometry-Based Redox and Protein Profiling of Failing Human Hearts

Tomin

Schittmayer

Sedej

et al. 2021

IJMS

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Oxidative stress contributes to detrimental functional decline of the myocardium, leading to the impairment of the antioxidative defense, dysregulation of redox signaling, and protein damage. In order to precisely dissect the changes of the myocardial redox state correlated with oxidative stress and heart failure, we subjected left-ventricular tissue specimens collected from control or failing human hearts to comprehensive mass spectrometry-based redox and quantitative proteomics, as well as glutathione status analyses. As a result, we report that failing hearts have lower glutathione to glutathione disulfide ratios and increased oxidation of a number of different proteins, including constituents of the contractile machinery as well as glycolytic enzymes. Furthermore, quantitative proteomics of failing hearts revealed a higher abundance of proteins responsible for extracellular matrix remodeling and reduced abundance of several ion transporters, corroborating contractile impairment. Similar effects were recapitulated by an in vitro cell culture model under a controlled oxygen atmosphere. Together, this study provides to our knowledge the most comprehensive report integrating analyses of protein abundance and global and peptide-level redox state in end-stage failing human hearts as well as oxygen-dependent redox and global proteome profiles of cultured human cardiomyocytes.

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“…In the past decade, numerous studies have found that some regulatory mechanisms, including cellular metabolism [ 13 ], proliferation [ 6 ], miRNAs [ 14 – 16 ], immune responses [ 17 , 18 ], translational regulation [ 19 ], and epigenetic modifications [ 20 , 21 ], positively or negatively regulate CH. Global transcriptome analyses have identified a few lncRNAs that are critically involved in CH [ 22 – 24 ].…”

Section: Introductionmentioning

confidence: 99%

The function of LncRNA-H19 in cardiac hypertrophy

Huo

Wang

et al. 2021

Cell Biosci

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Cardiac hypertrophy, characterized by the enlargement of cardiomyocytes, is initially an adaptive response to physiological and pathological stimuli. Decompensated cardiac hypertrophy is related to fibrosis, inflammatory cytokine, maladaptive remodeling, and heart failure. Although pathological myocardial hypertrophy is the main cause of hypertrophy-related morbidity and mortality, our understanding of its mechanism is still poor. Long noncoding RNAs (lncRNAs) are noncoding RNAs that regulate various physiological and pathological processes through multiple molecular mechanisms. Recently, accumulating evidence has indicated that lncRNA-H19 is a potent regulator of the progression of cardiac hypertrophy. For the first time, this review summarizes the current studies about the role of lncRNA-H19 in cardiac hypertrophy, including its pathophysiological processes and underlying pathological mechanism, including calcium regulation, fibrosis, apoptosis, angiogenesis, inflammation, and methylation. The context within which lncRNA-H19 might be developed as a target for cardiac hypertrophy treatment is then discussed to gain better insight into the possible biological functions of lncRNA-H19 in cardiac hypertrophy.

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Translating Translation to Mechanisms of Cardiac Hypertrophy

Cited by 19 publications

References 138 publications

Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs)

Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs)

Mass Spectrometry-Based Redox and Protein Profiling of Failing Human Hearts

The function of LncRNA-H19 in cardiac hypertrophy

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