ERKs and JNKs Mediate Hydrogen Peroxide-Induced Egr-1
Expression and Nuclear Accumulation in H9c2 Cells

Aggeli, Ioanna Katerina; Beis, Isidoros; Gaitanaki, Catherine

doi:10.33549/physiolres.931806

Cited by 24 publications

(2 citation statements)

References 45 publications

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“…Previous observations report that exogenous ROS administration to H9c2 cardiomyoblasts stimulated the c-Jun N-terminal kinase (JNK), a well-known member of MAPKs [ 112 ]. In experiments in H9c2 cardiomyocytes, metformin administration inhibited the mitochondrial overproduction of ROS induced by high glucose plus hypoxia/re-oxygenation injury, via signaling mechanisms involving activation of AMPK and concomitant inhibition of JNK expression [ 113 ].…”

Section: Mechanisms Of Beneficial Impact Of Metformin On Heart Failurementioning

confidence: 99%

Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence

et al. 2021

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Type 2 diabetes mellitus (T2DM) is a worldwide major health burden and heart failure (HF) is the most common cardiovascular (CV) complication in affected patients. Therefore, identifying the best pharmacological approach for glycemic control, which is also useful to prevent and ameliorate the prognosis of HF, represents a crucial issue. Currently, the choice is between the new drugs sodium/glucose co-transporter 2 inhibitors that have consistently shown in large CV outcome trials (CVOTs) to reduce the risk of HF-related outcomes in T2DM, and metformin, an old medicament that might end up relegated to the background while exerting interesting protective effects on multiple organs among which include heart failure. When compared with other antihyperglycemic medications, metformin has been demonstrated to be safe and to lower morbidity and mortality for HF, even if these results are difficult to interpret as they emerged mainly from observational studies. Meta-analyses of randomized controlled clinical trials have not produced positive results on the risk or clinical course of HF and sadly, large CV outcome trials are lacking. The point of force of metformin with respect to new diabetic drugs is the amount of data from experimental investigations that, for more than twenty years, still continues to provide mechanistic explanations of the several favorable actions in heart failure such as, the improvement of the myocardial energy metabolic status by modulation of glucose and lipid metabolism, the attenuation of oxidative stress and inflammation, and the inhibition of myocardial cell apoptosis, leading to reduced cardiac remodeling and preserved left ventricular function. In the hope that specific large-scale trials will be carried out to definitively establish the metformin benefit in terms of HF failure outcomes, we reviewed the literature in this field, summarizing the available evidence from experimental and clinical studies reporting on effects in heart metabolism, function, and structure, and the prominent pathophysiological mechanisms involved.

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Section: Mechanisms Of Beneficial Impact Of Metformin On Heart Failurementioning

confidence: 99%

Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence

et al. 2021

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“…EGR-1 is among those transcription factors classically activated by oxidative stress (202). Even subtle changes in the physiological redox status of the cell can lead to activation of EGR-1 signaling pathways (3,68,89,208,234). Once activated, EGR-1 binds to GC-rich cis-acting elements in promoters of target genes, regulating their expression (29).…”

Section: Egrmentioning

confidence: 99%

Nuclear Factor Kappa B Signaling Complexes in Acute Inflammation

Rius‐Pérez

Pérez

Martí‐Andrés

et al. 2020

Antioxidants & Redox Signaling

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Significance: NF-κB is a master regulator of the inflammatory response and represents a key regulatory node in the complex inflammatory signaling network. Additionally, selective NF-κB transcriptional activity on specific target genes occurs through the control of redox-sensitive NF-κB interactions.Critical issues: NF-κB is a redox-sensitive transcription factor that forms specific signaling complexes to regulate selectively the expression of target genes in acute inflammation. Protein-protein interactions with co-regulatory proteins, other transcription factors, and chromatin remodelling proteins provide transcriptional specificity to NF-κB. Furthermore, different NF-κB subunits may form distinct redoxsensitive homo and heterodimers with distinct affinities for κB sites. Recent advances:The selective NF-κB response is mediated by redox-modulated NF-κB complexes with RPS3, PIR. CBP/p300, PGC-1, AP-1, STAT3, EGR-1 and SP-1. NF-κB is cooperatively co-activated with AP-1, STAT3, EGR-1 and SP-1 during the inflammatory process, whereas NF-κB complexes with CBP/p300 and PGC-1α regulates the expression of antioxidant genes. p65 and Nrf2 compete for binding to coactivator CBP/p300 playing opposite roles in the regulation of inflammatory genes. Snitrosylation or tyrosine nitration favors the recruitment of specific NF-κB subunits to κB sites. Future directions:Further research is required to elucidate the whole NF-κB interactome in order to fully characterize the complex NF-κB signalling network in redox signaling, inflammation, and cancer.

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Egr‐1 transcriptionally activates protein phosphatase PTP1B to facilitate hyperinsulinemia‐induced insulin resistance in the liver in type 2 diabetes

Tao

et al. 2019

FEBS Letters

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During the development of type 2 diabetes mellitus (T2DM), hyperinsulinemia is the earliest symptom. It is believed that long‐term high insulin stimulation might facilitate insulin resistance in the liver, but the underlying mechanism remains unknown. Herein, we report that hyperinsulinemia could induce persistent early growth response gene‐1 (Egr‐1) activation in hepatocytes, which provides negative feedback inhibition of insulin sensitivity by inducing the expression of protein tyrosine phosphatase‐1B (PTP1B). Deletion of Egr‐1 in the liver remarkably decreases glucose production, thus improving systemic glucose tolerance and insulin sensitivity. Mechanistic analysis indicates that Egr‐1 inhibits insulin receptor phosphorylation by directly activating PTP1B transcription in the liver. Our results reveal the molecular mechanism by which hyperinsulinemia accelerates insulin resistance in hepatocytes during the progression of T2DM.

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ERKs and JNKs Mediate Hydrogen Peroxide-Induced Egr-1 Expression and Nuclear Accumulation in H9c2 Cells

Cited by 24 publications

References 45 publications

Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence

Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence

Nuclear Factor Kappa B Signaling Complexes in Acute Inflammation

Egr‐1 transcriptionally activates protein phosphatase PTP1B to facilitate hyperinsulinemia‐induced insulin resistance in the liver in type 2 diabetes

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