Identification of transcriptome signature for myocardial reductive stress

Redox Biology
Justin M QuilesNamakkal S Rajasekaran

Abstract

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

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Citations

Feb 15, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Jessica M MillerRamaswamy Kannappan
Feb 18, 2020·Antioxidants & Redox Signaling·Gobinath ShanmugamRajasekaran Namakkal Soorappan
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Jun 9, 2021·Scientific Reports·Justin M QuilesNamakkal S Rajasekaran

Methods Mentioned

BETA
ubiquitination
nuclear translocation
transgenic
RNAseq
protein folding
PCR

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