Role of myofibrillogenesis regulator-1 in myocardial hypertrophy

Li, Xiuhua; Li, Tianbo; Sun, Shuhan; Xu, Feifei; Wang, Yiguang

doi:10.1152/ajpheart.00247.2005

Cited by 16 publications

(23 citation statements)

References 17 publications

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“…Indeed, our previous study showed that MR-1 expression was in-duced in angiotensin II (Ang II)-treated cardiomyocytes and hypertrophied myocardium, whereas knockdown the expression of MR-1 prevented Ang II-induced hypertrophy. 5 These findings suggest that MR-1 plays an important role in Ang II-induced cardiac hypertrophy. However, to date, the mechanism of MR-1 on cardiac hypertrophy remains unclear.…”

mentioning

confidence: 88%

“…Probes of MR-1 (human and mouse), ANP, and BNP cDNA were generated by reverse transcription of heart mRNA and amplification of the resulting cDNA by the PCR, as described previously. 5,8 Protein extracts from different groups of myocardium (50 g) were fractionated on a 10% polyacrylamide gel under reducing conditions, transferred to nitrocellulose membranes, and probed with various antibodies. After incubation with a secondary peroxidase-conjugated antibody, signals were visualized by Chemiluminescence kit (Amersham).…”

Section: Northern Blot and Western Blot Analysismentioning

confidence: 99%

“…We generated recombinant adenoviral vectors encoding MR-1 and MR-1 silencing RNA using the small interference (si)RNA sequence described previously 5 and expanded them in 293 cells. Control adenoviral GFP was produced as described previously.…”

Section: Electrophoretic Mobility Shift Assay and Inhibitor Of Nucleamentioning

confidence: 99%

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Overexpression of Myofibrillogenesis Regulator-1 Aggravates Cardiac Hypertrophy Induced by Angiotensin II in Mice

She

et al. 2007

Hypertension

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Abstract-Myofibrillogenesis regulator-1 (MR-1) augments cardiomyocytes hypertrophy induced by angiotensin II (Ang II) in vitro. However, its roles in cardiac hypertrophy in vivo remain unknown. Here, we investigate whether MR-1 can promote cardiac hypertrophy induced by Ang II in vivo and elucidate the molecular mechanisms of MR-1 on cardiac hypertrophy. We used a model of Ang II-induced cardiac hypertrophy by infusion of Ang II in female mice. In wild-type mice subjected to the Ang II infusion, cardiac hypertrophy developed after 2 weeks. In mice overexpressing human MR-1 (transgenic), however, cardiac hypertrophy was significantly greater than in wild-type mice as estimated by heart weight:body weight ratio, cardiomyocyte area, and echocardiographic measurements, as well as cardiac atrial natriuretic peptide and B-type natriuretic peptide mRNA and protein levels. Our further results showed that cardiac inflammation and fibrosis observed in wild-type Ang II mice were augmented in transgenic Ang II mice. Importantly, increased nuclear factor B activation was significantly increased higher in transgenic mice compared with wild-type mice after 2 weeks of Ang II infusion. In vitro experiments also revealed that overexpression of MR-1 enhanced Ang II-induced nuclear factor B activation, whereas downregulation of MR-1 blocked it in cardiac myocytes. In conclusion, our results suggest that MR-1 plays an aggravative role in the development of cardiac hypertrophy via activation of the nuclear factor B signaling pathway. Key Words: hypertrophy Ⅲ myocardium Ⅲ NF-B Ⅲ myofibrillogenesis regulator-1 Ⅲ fibrosis Ⅲ angiotensin II T he heart undergoes adaptive hypertrophic growth to augment cardiac output in response to a variety of pathological stimulations, including hypertension, myocardial infarction, pressure overload, and abnormalities in contractility and structure because of inherited gene mutations. 1,2 Although initial cardiac hypertrophy acts like an adaptive mechanism, prolonged and severe hypertrophy is a risk factor for arrhythmias, sudden death, and heart failure. Because cardiac hypertrophy is a highly complex disorder that results from an interaction of genetic, physiological, and environmental factors, many genes and their products participated in its pathogenesis through different pathways. 1,2 Therefore, the discovery and functional clarification of cardiac hypertrophyrelated novel human genes are important for understanding the molecular mechanisms underlying cardiac hypertrophy.Myofibrillogenesis regulator-1 (MR-1) was identified from a human skeletal muscle cDNA library, which encodes a protein of 142 amino acids with a hydrophobic transmembrane structure from 75 to 92 amino acids. 3 MR-1 protein is mainly located on the nucleic membrane and, to a lesser extent, in the cytoplasm. Northern blot and serial analysis of gene expression revealed that the transcription level of MR-1 in human tissues is especially high in myocardium and skeletal muscle. 3 Yeast 2-hybrid screening and in vitro glutathione S-transf...

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confidence: 88%

Section: Northern Blot and Western Blot Analysismentioning

confidence: 99%

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Overexpression of Myofibrillogenesis Regulator-1 Aggravates Cardiac Hypertrophy Induced by Angiotensin II in Mice

She

et al. 2007

Hypertension

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“…Protein was extracted from renal tissue or cells as previously described [16]. Protein concentration in the detergent soluble supernatant was determined by the Bradford method [17].…”

Section: Methodsmentioning

confidence: 99%

Kidney Protection against Ischemia/Reperfusion Injury by Myofibrillogenesis Regulator-1

Wang

Tao²,

Ding³

et al. 2014

Am J Nephrol

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Background/Aims: Ischemia/reperfusion (I/R) injury is characterized by cytoskeletal reorganization and loss of polarity in proximal tubule epithelial cells. Previously, we showed that myofibrillogenesis regulator (MR)-1 promoted actin organization in cardiomyocytes. MR-1 is also expressed in the kidney. Methods: In this study, we investigated MR-1 expression in acute renal failure induced by I/R in Sprague-Dawley rats. We determined the MR-1 expression and the ratio of fibrous actin (F-actin) to globular actin (G-actin). HK-2 cells were treated with or without hypoxia/reoxygenation (H/R), and MR-1 levels were increased by adenoviral overexpression or silenced by RNA interference. Results: I/R and H/R resulted in cellular injury and decreases of MR-1, the F-/G-actin ratio, and myosin light chain (MLC)-2. MR-1 overexpression attenuated H/R-induced cell injury and loss of surface membrane polarity of actin. MR-1 overexpression also increased the expression and phosphorylation of MLC-2 and MLC kinase, which were decreased in MR-1-silenced and H/R-treated cells. Conclusion: Together, these data show that MR-1 promoted actin polarity on the membrane surface and protected HK-2 cells from H/R injury. The mechanism might involve the rapid organization of F-actin through the upregulation and phosphorylation of MLC-2.

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“…The levels of analyzed proteins were normalized to that of GAPDH, which was calibrated to 1.0. 3 H]leucine incorporation was determined as previously described (25). Briefly, cells were washed with ice-cold PBS three times and incubated with formic acid for 30 min to lyse protein at room temperature.…”

Section: Cellmentioning

confidence: 99%

The calcineurin-myocyte enhancer factor 2c pathway mediates cardiac hypertrophy induced by endoplasmic reticulum stress in neonatal rat cardiomyocytes

Zhang

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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The calcineurin-myocyte enhancer factor 2c pathway mediates cardiac hypertrophy induced by endoplasmic reticulum stress in neonatal rat cardiomyocytes. Am J Physiol Heart Circ Physiol 298: H1499 -H1509, 2010. First published March 5, 2010; doi:10.1152/ajpheart.00980.2009.-Endoplasmic reticulum (ER) stress (ERS) is involved in various cardiovascular diseases. Our previous study verified that ERS took part in the development of cardiac hypertrophy; however, its mechanism is still unclear. This study aimed to investigate the roles of the calcineurin (CaN) signal pathway in hypertrophy induced by the ERS inductor thapsigargin (TG) in neonatal cardiomyocytes from Sprague-Dawley rats. Investigation of ER chaperone expression, ER staining, and calreticulin immunoflourescence were used to detect the ERS response. mRNA expression of atrial natriuretic peptide and brain natriuretic peptide, total protein synthesis rate, and cell surface area were used to evaluate cardiac hypertrophy induced by TG. TG induced a significant ERS response along with hypertrophy in a doseand time-dependent manner in cardiomyocytes, which was verified by treatment with tunicamycin, another ERS inducer. Furthermore, TG induced a significant elevation of the intracellular Ca 2ϩ level, CaN activation, and myocyte enhancer factor 2c (MEF2c) expression in a dose-and time-dependent manner in cardiomyocytes. Cyclosporine A, a CaN inhibitor, markedly suppressed MEF2c nuclear translocation and inhibited TG-induced hypertrophy. These results demonstrate that ERS induces cardiac hypertrophy and that the CaN-MEF2c pathway is involved in ERS-induced hypertrophy in cardiomyocytes. thapsigargin CARDIAC HYPERTROPHY is an adaptive response triggered by many physiological and pathological conditions. However, epidemiological data have indicated that chronic cardiac hypertrophy is associated with an increase in the cardiovascular morbidity/mortality risk. Evidence has shown that many factors, including Ca 2ϩ overload, abnormal protein synthesis, and apoptosis, are involved in the development of cardiac hypertrophy (20). The endoplasmic reticulum (ER), called the sarcoplasmic reticulum (SR) in cardiac myocytes, is an organelle regulating intracellular Ca 2ϩ , folding of secreted and membrane protein, and cell apoptosis. Various stimuli, such as ER Ca 2ϩ depletion, elevated protein synthesis, ischemia, and hypoxia, disturb ER homeostasis and result in ER stress (ERS). In response to ERS, ER chaperones such as calreticulin (CRT) and glucose-regulated proteins (GRPs) are upregulated to enhance the ability of the ER to regulate the intracellular Ca 2ϩ level and handle the unfolded proteins, which is cardioprotective. However, when ERS is excessive and/or prolonged, the ER-related apoptotic process is initiated by the induction of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) and caspase-12 activation. Protein kinase R-like ER kinase (PERK) is an important ER transmembrane protein; the relocation of GRP78 from the luminal domain of PERK to misfolded ...

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Role of myofibrillogenesis regulator-1 in myocardial hypertrophy

Cited by 16 publications

References 17 publications

Overexpression of Myofibrillogenesis Regulator-1 Aggravates Cardiac Hypertrophy Induced by Angiotensin II in Mice

Overexpression of Myofibrillogenesis Regulator-1 Aggravates Cardiac Hypertrophy Induced by Angiotensin II in Mice

Kidney Protection against Ischemia/Reperfusion Injury by Myofibrillogenesis Regulator-1

The calcineurin-myocyte enhancer factor 2c pathway mediates cardiac hypertrophy induced by endoplasmic reticulum stress in neonatal rat cardiomyocytes

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