Injury-induced mineralocorticoid receptor expression involves differential promoter usage: a novel role for the rat MRbeta variant.
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 (alpha, beta, gamma) each with unique promoters and a common coding region. We examined whether distinct cellular stressors differentially regulate exon-specific MR transcripts. MRbeta 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 MRbeta promoter activity. A specific increase in MRbeta transcript expression was also found in vivo in hypothermic anoxic neonatal rat hippocampus. These results demonstrate a novel key role for the MRbeta transcript in response to injury and suggest that some of the known neuroprotective effects of hypothermia may be mediated through increased MR expression.
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Scotland, UK.
Peng
P
Kang
Justyna
J
Rogalska
Catherine A
CA
Walker
Matthew
M
Burke
Jonathan R
JR
Seckl
Malcolm R
MR
Macleod
Maggie
M
Lai
D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D003080:Cold Temperature; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D020935:MAP Kinase Signaling System; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D005947:Glucose