The nuclear factor erythroid 2 like 2 (Nfe2l2/Nrf2) is a master regulator of antioxidant gene transcription. We recently identified that constitutive activation of Nrf2 (CaNrf2) caused reductive stress (RS) in the myocardium. Here we investigate how chronic Nrf2 activation alters myocardial mRNA transcriptome in the hearts of CaNrf2 transgenic (TG-low and TG-high) mice using an unbiased integrated systems approach and next generation RNA sequencing followed by qRT-PCR methods. A total of 246 and 1031 differentially expressed genes (DEGs) were identified in the heart of TGL and TGH in relation to NTG littermates at ~ 6 months of age. Notably, the expression and validation of the transcripts were gene-dosage dependent and statistically significant. Ingenuity Pathway Analysis identified enriched biological processes and canonical pathways associated with myocardial RS in the CaNrf2-TG mice. In addition, an overrepresentation of xenobiotic metabolic signaling, glutathione-mediated detoxification, unfolded protein response, and protein ubiquitination was observed. Other, non-canonical signaling pathways identified include: eNOS, integrin-linked kinase, glucocorticoid receptor, PI3/AKT, actin cytoskeleton, cardiac hypertrophy, and th...Continue Reading
Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology
Cardiac ankyrin repeat protein, a negative regulator of cardiac gene expression, is augmented in human heart failure
Reversible S-glutathionylation of Cys 374 regulates actin filament formation by inducing structural changes in the actin molecule
Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms
Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression.
Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress.
Increased plasma non-esterified fatty acids and platelet-activating factor acetylhydrolase are associated with susceptibility to atherosclerosis in mice
Expression of SCC-S2, an antiapoptotic molecule, correlates with enhanced proliferation and tumorigenicity of MDA-MB 435 cells
Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes
PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress.
Decline of contractility during ischemia-reperfusion injury: actin glutathionylation and its effect on allosteric interaction with tropomyosin
Integrin-linked kinase expression is elevated in human cardiac hypertrophy and induces hypertrophy in transgenic mice
Capsaicin induces heme oxygenase-1 expression in HepG2 cells via activation of PI3K-Nrf2 signaling: NAD(P)H:quinone oxidoreductase as a potential target
Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets
The Kruppel-like factor KLF15 inhibits connective tissue growth factor (CTGF) expression in cardiac fibroblasts
Oncogene AF1q enhances doxorubicin-induced apoptosis through BAD-mediated mitochondrial apoptotic pathway
Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungs
Actin isoform expression patterns during mammalian development and in pathology: insights from mouse models
IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates
Reticulon-4A (Nogo-A) redistributes protein disulfide isomerase to protect mice from SOD1-dependent amyotrophic lateral sclerosis
The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1
Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1
Mice with tissue inhibitor of metalloproteinases 4 (Timp4) deletion succumb to induced myocardial infarction but not to cardiac pressure overload.
Early activation of matrix metalloproteinases underlies the exacerbated systolic and diastolic dysfunction in mice lacking TIMP3 following myocardial infarction
Sustained activation of nuclear erythroid 2-related factor 2/antioxidant response element signaling promotes reductive stress in the human mutant protein aggregation cardiomyopathy in mice
Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle
Induction of glutathione synthesis and heme oxygenase 1 by the flavonoids butein and phloretin is mediated through the ERK/Nrf2 pathway and protects against oxidative stress
Long-term antioxidant supplementation has no effect on health-related quality of life: the randomized, double-blind, placebo-controlled, primary prevention SU.VI.MAX trial
IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress
G-protein inactivator RGS6 mediates myocardial cell apoptosis and cardiomyopathy caused by doxorubicin
Characterization of recombinant ELMOD (cell engulfment and motility domain) proteins as GTPase-activating proteins (GAPs) for ARF family GTPases.
The translation elongation factor eEF1A1 couples transcription to translation during heat shock response
Estrogen and testosterone in concert with EFNB3 regulate vascular smooth muscle cell contractility and blood pressure
Protective role of melatonin in cardiac ischemia-reperfusion injury: From pathogenesis to targeted therapy
Exercise Mediated Nrf2 Signaling Protects the Myocardium From Isoproterenol-Induced Pathological Remodeling
Identification of signal pathways for immunotoxicity in the spleen of common carp exposed to chlorpyrifos
Identification of Nrf2-responsive microRNA networks as putative mediators of myocardial reductive stress.
Implications of Oxidative and Nitrosative Post-Translational Modifications in Therapeutic Strategies against Reperfusion Damage.
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