Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-2-9
pubmed:abstractText
Specific arrays and timing of environmental cues including glucocorticoids, neurotrophic factors and intracellular messengers influence phenotype expression in developing chromaffin cells or sympathetic neurons. Although the two lineages are closely related, only adrenergic chromaffin cells express phenylethanolamine N-methyltransferase (PNMT), the enzyme that synthesizes epinephrine, while neurons and noradrenergic chromaffin cells are PNMT-negative. It remains unclear to what extent the ability to express PNMT is determined by environmental cues versus intrinsic heterogeneity already present in ganglionic and adrenal precursors. Mouse pheochromocytoma (MPC) cell lines are a model for studying adrenergic differentiation. In two MPC lines that exhibit up to 1000-fold induction of PNMT mRNA by dexamethasone, pretreatment with glial cell line-derived neurotrophic factor (GDNF) and/or the cyclic AMP analog cpt-cAMP markedly blunts or abrogates PNMT inducibility. PNMT suppression occurs without apparent neuronal differentiation in one of the MPC lines and in normal adult mouse chromaffin cell cultures. Our results establish transcriptional suppression by cAMP as a mechanism for regulating PNMT expression in both normal and neoplastic mouse chromaffin cells. However, contrast between large increases in PNMT mRNA levels and low stimulation of promoter activity suggests that modulation of mRNA degradation also plays an important role. Clarification of mechanisms that regulate these two processes in MPC cells may provide insight into developmental mechanisms governing expression and maintenance of the adrenergic phenotype.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
313
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
772-81
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Transcriptional silencing of glucocorticoid-inducible phenylethanolamine N-methyltransferase expression by sequential signaling events.
pubmed:affiliation
Department of Pediatrics, Stony Brook University, Stony Brook, NY, USA. mevinger@notes.cc.sunysb.edu <mevinger@notes.cc.sunysb.edu>
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural