Effects of MEK5/ERK5 Association on Small Ubiquitin-Related Modification of ERK5: Implications for Diabetic Ventricular Dysfunction After Myocardial Infarction

Shishido, Tetsuro; Woo, Chang Hoon; Ding, Bo; McClain, Carolyn; Molina, Carlos A.; Yan, Chen; Yang, Jay; Abe, Jun

doi:10.1161/circresaha.107.168138

Cited by 74 publications

(85 citation statements)

References 21 publications

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“…ERK5 is an atypical mitogen-activated protein kinase functioning as a transcriptional co-activator for PPARs and MEF2 in the heart. [95][96][97] SUMOylation of ERK5, which is strongly induced in diabetic animals, dampens its transcriptional activity. In diabetic mice, this was linked to ventricular dysfunction after myocardial infarction.…”

mentioning

confidence: 99%

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The Ubiquitin-Like SUMO System and Heart Function

Mendler

Braun

Müller

2016

Circulation Research

101

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confidence: 99%

“…In diabetic mice, this was linked to ventricular dysfunction after myocardial infarction. 96 Acetylation/deacetylation represents a different way to regulate the activity of PPARs and PGC-1α. Sirtuin 1 (SIRT1), an NAD + -dependent histone deacetylase (HDAC), plays an important role in cardiac metabolism.…”

mentioning

confidence: 99%

The Ubiquitin-Like SUMO System and Heart Function

Mendler

Braun

Müller

2016

Circulation Research

101

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“…However, these geometric changes were attenuated in MK-KO mice when compared with those observed in WT mice (Table S1). We also performed terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining and Masson trichrome staining to evaluate the degree of apoptosis 26 and fibrosis 27 occurring in the heart after nephrectomy. However, no significant differences in the degrees of apoptosis and fibrosis between MK-KO and WT mice were observed ( Figure S6).…”

Section: Effects Of Subtotal Nephrectomy On Cardiac Hypertrophy In Mkmentioning

confidence: 99%

“…Total proteins were extracted from the left ventricle, lung, and kidney using ice-cold lysis buffer, as described previously 3 . The protein concentrations of each sample were determined using the BCA protein assay (BioRad Laboratories, Inc., Hercules, CA).…”

Section: Primary Culture Of Neonatal Rat Cardiomyocytesmentioning

confidence: 99%

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Midkine Deteriorates Cardiac Remodeling via Epidermal Growth Factor Receptor Signaling in Chronic Kidney Disease

et al. 2016

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Abstract-In chronic kidney disease, activation of the epidermal growth factor receptor (EGFR) leads to cardiac hypertrophy, which affects morbidity and mortality. In patients with renal insufficiency and heart failure, the expression of midkine, a heparin-binding growth factor, is increased. Therefore, we investigated the association between midkine and EGFR in the induction of cardiac hypertrophy and dysfunction in chronic kidney disease. We performed subtotal nephrectomies in midkine-knockout mice and wild-type mice. We found that subtotal nephrectomy-induced cardiac hypertrophy and phosphorylation of extracellular signal-regulated kinase 1/2 and AKT were attenuated in midkine-knockout mice compared with wild-type mice. An antiphosphotyrosine receptor antibody array was used to demonstrate that EGFR phosphorylation in the heart was also lower in midkine-knockout mice than in wild-type mice. Midkine induced EGFR, extracellular signal-regulated kinase 1/2, and AKT phosphorylation and led to hypertrophy in neonatal rat cardiomyocytes. Pretreatment with EGFR inhibitors or EGFR silencing suppressed midkine-stimulated phosphorylation of extracellular signal-regulated kinase 1/2 and AKT, induction of fetal cardiac gene expression, and hypertrophy in cardiomyocytes.To confirm the association between midkine and EGFR in vivo, mice subjected to subtotal nephrectomy were treated with the EGFR inhibitor gefitinib. Gefitinib treatment attenuated subtotal nephrectomy-induced cardiac hypertrophy. These results indicate that midkine might be a key mediator of cardiorenal interactions through EGFR activation, which plays a crucial role in cardiac hypertrophy in chronic kidney disease. (Hypertension. 2016;67:857-865.

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mAKAPβ signalosome: A potential target for cardiac hypertrophy

Golatkar,

Bhatt

2023

Drug Development Research

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Pathological cardiac hypertrophy is the result of a prolonged increase in the workload of the heart that activates various signaling pathways such as MAPK pathway, PKA‐dependent cAMP signaling, and CaN‐NFAT signaling pathway which further activates genes for cardiac remodeling. Various signalosomes are present in the heart that regulates the signaling of physiological and pathological cardiac hypertrophy. mAKAPβ is one such scaffold protein that regulates signaling pathways involved in promoting cardiac hypertrophy. It is present in the outer nuclear envelope of the cardiomyocytes, which provides specificity of the target toward the heart. In addition, nuclear translocation of signaling components and transcription factors such as MEF2D, NFATc, and HIF‐1α is facilitated due to the localization of mAKAPβ near the nuclear envelope. These factors are required for activation of genes promoting cardiac remodeling. Downregulation of mAKAPβ improves cardiac function and attenuates cardiac hypertrophy which in turn prevents the development of heart failure. Unlike earlier therapies for heart failure, knockout or silencing of mAKAPβ is not associated with side effects because of its high specificity in the striated myocytes. Downregulating expression of mAKAPβ is a favorable therapeutic approach toward attenuating cardiac hypertrophy and hence preventing heart failure. This review discusses mAKAPβ signalosome as a potential target for cardiac hypertrophy intervention.

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Effects of MEK5/ERK5 Association on Small Ubiquitin-Related Modification of ERK5: Implications for Diabetic Ventricular Dysfunction After Myocardial Infarction

Cited by 74 publications

References 21 publications

The Ubiquitin-Like SUMO System and Heart Function

The Ubiquitin-Like SUMO System and Heart Function

Midkine Deteriorates Cardiac Remodeling via Epidermal Growth Factor Receptor Signaling in Chronic Kidney Disease

mAKAPβ signalosome: A potential target for cardiac hypertrophy

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