Injury-induced mineralocorticoid receptor expression involves differential promoter usage: A novel role for the rat MRβ variant

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Neuronal injury results in increased mineralocorticoid receptor (MR) expression and is associated with increased neuronal survival, suggesting that enhancing MR signalling may have therapeutic implications. MR has a complex gene structure with at least three untranslated exons (α, β, γ) each with unique promoters and a common coding region. We examined whether distinct cellular stressors differentially regulate exon-specific MR transcripts. MRβ transcript was specifically upregulated in rat primary cortical cultures undergoing hypothermic oxygen-glucose deprivation (OGD/H) through activation of its own promoter. This effect was mediated in part by ERK signalling as blockade with PD98059 inhibited OGD/H-induced MRβ promoter activity. A specific increase in MRβ transcript expression was also found in vivo in hypothermic anoxic neonatal rat hippocampus. These results demonstrate a novel key role for the MRβ transcript in response to injury and suggest that some of the known neuroprotective effects of hypothermia may be mediated through increased MR expression.

Functional characterization of chicken glucocorticoid and mineralocorticoid receptors

“…In rat MR, three distinct mRNA transcripts differing at the 5=UTR but encoding the same protein have been observed (30). Furthermore, deletion of 10 bp, resulting in truncation of the LBD in rat MR and differential expression of rat transcript variants in response to neuronal stress, have been also reported (27,67). Moreover, mammalian mRNA isoforms of MR show tissue-related expression (46,59,67).…”

A common and functional mineralocorticoid receptor haplotype enhances optimism and protects against depression in females

“…30, 31, 32, 33, 34, 35 Context-dependent changes in MR expression can be established by distinct 5′ MR mRNA transcripts (MRα and MRβ), each having its own promoter containing regulatory elements and showing differential expression depending on tissue, time and availability of steroids and stress. 6, 30, 36, 37, 38 SNPs may result in differential expression of MRα vs MRβ by affecting TF binding or splicing. Two of the eight common 5′ UTR SNPs were consistently predicted to influence TF binding while a third SNP was predicted to affect a glucocorticoid responsive element-consensus sequence (although not consistent).…”

The expression profile of genes associated with behavior, stress, and adult neurogenesis along the hippocampal dorsoventral axis in tame and aggressive foxes

“…differences amongst groups in the expression of a particular splice variant will be more pronounced. It has been shown that their expression in cellular stress in a primary culture of cortex cells varies irregularly (Kang et al, 2009). Here we analyze only the total pool of NR3C2 mRNA, because the fox genome had not been annotated in sufficient detail.…”