scholarly journals Soluble Epoxide Hydrolase Inhibitors Regulate Ischemic Arrhythmia by Targeting MicroRNA-1

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanying Chen ◽  
Qiong Liu ◽  
Tian Yang ◽  
Li Shen ◽  
Danyan Xu
Keyword(s):  
Epoxide Hydrolase ◽  
Target Genes ◽  
Serum Response Factor ◽  
Soluble Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase Inhibitors ◽  
Interfering Rna ◽  
Serum Response ◽  
Ischemic Arrhythmia ◽  
Antiarrhythmic Effects

Background: Soluble epoxide hydrolase inhibitors (sEHis) inhibit the degradation of epoxyeicosatrienoic acids (EETs) in cells, and EETs have antiarrhythmic effects. Our previous experiments confirmed that t-AUCB, a preparation of sEHis, inhibited ischemic arrhythmia by negatively regulating microRNA-1 (miR-1), but its specific mechanism remained unclear.Aim: This study aimed to examine the role of serum response factor (SRF) and the PI3K/Akt/GSK3β pathway in t-AUCB-mediated regulation of miR-1 and the interaction between them.Methods/Results: We used SRF small interfering RNA (siSRF), SRF small hairpin (shSRF) RNA sequence adenovirus, PI3K/Akt/GSK3β pathway inhibitors, t-AUCB, and 14,15-EEZE (a preparation of EETs antagonists) to treat mouse cardiomyocytes overexpressing miR-1 and mice with myocardial infarction (MI). We found that silencing SRF attenuated the effects on miR-1 and its target genes KCNJ2 and GJA1 in the presence of t-AUCB, and inhibition of the PI3K/Akt/GSK3β pathway antagonized the effects of t-AUCB on miR-1, KCNJ2, and GJA1, which were associated with PI3Kα, Akt, and Gsk3β but not PI3Kβ or PI3Kγ. Moreover, the PI3K/Akt/GSK3β pathway was involved in the regulation of SRF by t-AUCB, and silencing SRF inhibited the t-AUCB-induced increases in Akt and Gsk3β phosphorylation.Conclusions: Both the SRF and the PI3K/Akt/GSK3β pathway are involved in the t-AUCB-mediated regulation of miR-1, and these factors interact with each other.

scholarly journals Soluble epoxide hydrolase inhibitors, t-AUCB, regulated microRNA-1 and its target genes in myocardial infarction mice

Oncotarget ◽  
2017 ◽  
Vol 8 (55) ◽  
pp. 94635-94649 ◽  
Author(s):  
Ya-Jun Gui ◽  
Tao Yang ◽  
Qiong Liu ◽  
Cai-Xiu Liao ◽  
Jing-Yuan Chen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Epoxide Hydrolase ◽  
Target Genes ◽  
Soluble Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase Inhibitors

scholarly journals Lamina-associated polypeptide 2α is required for intranuclear MRTF-A activity

2021 ◽  
Author(s):  
Ekaterina Sidorenko ◽  
Maria Sokolova ◽  
Antti Pennanen ◽  
Salla Kyheroinen ◽  
Guido Posern ◽  
...  
Keyword(s):  
Target Genes ◽  
Serum Response Factor ◽  
Actin Dynamics ◽  
Chromatin Binding ◽  
Binding Partner ◽  
Related Transcription Factor ◽  
Direct Binding ◽  
Efficient Expression ◽  
Serum Response

Myocardin-related transcription factor A (MRTF-A), a coactivator of serum response factor (SRF), regulates the expression of many cytoskeletal genes in response to cytoplasmic and nuclear actin dynamics. Here we describe a novel mechanism to regulate MRTF-A activity within the nucleus by showing that lamina-associated polypeptide 2α (Lap2α), the nucleoplasmic isoform of Lap2, is a direct binding partner of MRTF-A, and required for the efficient expression of MRTF-A/SRF target genes. Mechanistically, Lap2α is not required for MRTF-A nuclear localization, unlike most other MRTF-A regulators, but is required for binding of MRTF-A to its target genes. This regulatory step takes place prior to MRTF-A chromatin binding, because Lap2α neither interacts with, nor specifically influences active histone marks on MRTF-A/SRF target genes. Phenotypically, Lap2α is required for serum-induced cell migration, and deregulated MRTF-A activity may also contribute to muscle and proliferation phenotypes associated with loss of Lap2α. Our studies therefore add another regulatory layer to the control of MRTF-A-SRF-mediated gene expression, and broaden the role of Lap2α in transcriptional regulation.

scholarly journals A Soluble Epoxide Hydrolase Inhibitor Upregulated KCNJ12 and KCNIP2 by Downregulating MicroRNA-29 in a Mouse Model of Myocardial Infarction

2020 ◽  
Vol 23 (5) ◽  
pp. E579-E585
Author(s):  
Xiaojun Zhang ◽  
Caixiu Liao ◽  
Kaijun Sun ◽  
Leiling Liu ◽  
Danyan Xu
Keyword(s):  
Myocardial Infarction ◽  
Protein Expression ◽  
Epoxide Hydrolase ◽  
Target Genes ◽  
Soluble Epoxide Hydrolase ◽  
Distilled Water ◽  
Expression Levels ◽  
Ischemic Region ◽  
Soluble Epoxide Hydrolase Inhibitors ◽  
Potential Therapeutic Application

Background: Soluble epoxide hydrolase inhibitors (sEHi) have anti-arrhythmic effects, and we previously found that the novel sEHi t-AUCB (trans-4[-4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid) significantly inhibited ventricular arrhythmias after myocardial infarction (MI). However, the mechanism is unknown. It’s known that microRNA-29 (miR-29) participates in the occurrence of arrhythmias. In this study, we investigated whether sEHi t-AUCB was protective against ischemic arrhythmias by modulating miR-29 and its target genes KCNJ12 and KCNIP2. Methods: Male 8-week-old C57BL/6 mice were divided into five groups and fed distilled water only or distilled water with t-AUCB of different dosages for seven days. Then, the mice underwent MI or sham surgery. The ischemic region of the myocardium was obtained 24 hours after MI to detect miR-29, KCNJ12, and KCNIP2 mRNA expression levels via real-time PCR and KCNJ12 and KCNIP2 protein expression levels via western blotting. Results: MiR-29 expression levels were significantly increased in the ischemic region of MI mouse hearts and the mRNA and protein expression levels of its target genes KCNJ12 and KCNIP2 were significantly decreased. T-AUCB prevented these changes dose-dependently. Conclusion: The sEHi t-AUCB regulates the expression levels of miR-29 and its target genes KCNJ12 and KCNIP2, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmia.

scholarly journals The Aging Vasculature: Glucose Tolerance, Hypoglycemia and the Role of the Serum Response Factor

2021 ◽  
Vol 8 (5) ◽  
pp. 58
Author(s):  
Hazel Aberdeen ◽  
Kaela Battles ◽  
Ariana Taylor ◽  
Jeranae Garner-Donald ◽  
Ana Davis-Wilson ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Molecular Mechanisms ◽  
Serum Response Factor ◽  
Response Factor ◽  
Homeostatic Control ◽  
Older Americans ◽  
The Subject ◽  
Serum Response

The fastest growing demographic in the U.S. at the present time is those aged 65 years and older. Accompanying advancing age are a myriad of physiological changes in which reserve capacity is diminished and homeostatic control attenuates. One facet of homeostatic control lost with advancing age is glucose tolerance. Nowhere is this more accentuated than in the high proportion of older Americans who are diabetic. Coupled with advancing age, diabetes predisposes affected subjects to the onset and progression of cardiovascular disease (CVD). In the treatment of type 2 diabetes, hypoglycemic episodes are a frequent clinical manifestation, which often result in more severe pathological outcomes compared to those observed in cases of insulin resistance, including premature appearance of biomarkers of senescence. Unfortunately, molecular mechanisms of hypoglycemia remain unclear and the subject of much debate. In this review, the molecular basis of the aging vasculature (endothelium) and how glycemic flux drives the appearance of cardiovascular lesions and injury are discussed. Further, we review the potential role of the serum response factor (SRF) in driving glycemic flux-related cellular signaling through its association with various proteins.

scholarly journals Critical Role of Serum Response Factor in Pulmonary Myofibroblast Differentiation Induced by TGF-β

2009 ◽  
Vol 41 (3) ◽  
pp. 332-338 ◽  
Author(s):  
Nathan Sandbo ◽  
Steven Kregel ◽  
Sebastien Taurin ◽  
Sangeeta Bhorade ◽  
Nickolai O. Dulin
Keyword(s):  
Serum Response Factor ◽  
Critical Role ◽  
Myofibroblast Differentiation ◽  
Response Factor ◽  
Serum Response

scholarly journals Role of soluble epoxide hydrolase phosphatase activity in the metabolism of lysophosphatidic acids

2012 ◽  
Vol 419 (4) ◽  
pp. 796-800 ◽  
Author(s):  
Christophe Morisseau ◽  
Nils Helge Schebb ◽  
Hua Dong ◽  
Arzu Ulu ◽  
Pavel A. Aronov ◽  
...  
Keyword(s):  
Phosphatase Activity ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase
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