Document Detail


Transcription factor AP-2β regulates the neurotransmitter phenotype and maturation of chromaffin cells.
MedLine Citation:
PMID:  20875861     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During development, sympathetic neurons and chromaffin cells originate from bipotential sympathoadrenal (SA) progenitors arising from neural crests (NC) in the trunk regions. Recently, we showed that AP-2β, a member of the AP2 family, plays a critical role in the development of sympathetic neurons and locus coeruleus and their norepinephrine (NE) neurotransmitter phenotype. In the present study, we investigated the potential role of AP-2β in the development of NC-derived neuroendocrine chromaffin cells of the adrenal medulla and the epinephrine (EPI) phenotype determination. In support of its role in chromaffin cell development, AP-2β is prominently expressed in both embryonic and adult adrenal medulla. In adrenal chromaffin cells of the AP-2β(-/-) mouse, the expression levels of catecholamine biosynthesizing enzymes, dopamine β-hydroxylase (DBH) and phenylethanolamine-N-methyl-transferase (PNMT), as well as the SA-specific transcription factor, Phox2b, are significantly reduced compared to wild type. In addition, ultrastructural analysis demonstrated that the formation of large secretory vesicles, a hallmark of differentiated chromaffin cells, is defective in AP-2β(-/-) mice. Furthermore, the level of EPI content is largely diminished (>80%) in the adrenal gland of AP-2β(-/-) mice. Chromatin immunoprecipitation (ChIP) assays of rat adrenal gland showed that AP-2β binds to the upstream promoter of the PNMT gene in vivo; strongly suggesting that it is a direct target gene. Overall, our data suggest that AP-2β plays critical roles in the epinephrine phenotype and maturation of adrenal chromaffin cells.
Authors:
Seok Jong Hong; Yang Hoon Huh; Amanda Leung; Hyun Jin Choi; Yunmin Ding; Un Jung Kang; Seung Hyun Yoo; Reinhard Buettner; Kwang-Soo Kim
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-09-27
Journal Detail:
Title:  Molecular and cellular neurosciences     Volume:  46     ISSN:  1095-9327     ISO Abbreviation:  Mol. Cell. Neurosci.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-10     Completed Date:  2011-07-05     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  9100095     Medline TA:  Mol Cell Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  245-51     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adrenal Glands / cytology,  metabolism
Adrenergic Fibers / metabolism
Animals
Chromaffin Cells / cytology,  physiology*
Epinephrine / metabolism
Female
Gene Expression
Mice
Mice, Knockout
Neurotransmitter Agents / metabolism*
Norepinephrine / metabolism
Phenotype*
Phenylethanolamine N-Methyltransferase / genetics,  metabolism
Promoter Regions, Genetic
Rats
Secretory Vesicles / ultrastructure
Transcription Factor AP-2 / genetics,  metabolism*
Tyrosine 3-Monooxygenase / metabolism
Grant Support
ID/Acronym/Agency:
MH087903/MH/NIMH NIH HHS; MH48866/MH/NIMH NIH HHS; R01 MH048866/MH/NIMH NIH HHS; R01 MH048866-21/MH/NIMH NIH HHS; R01 NS053919/NS/NINDS NIH HHS; R01 NS053919-04/NS/NINDS NIH HHS; R21 MH087903/MH/NIMH NIH HHS; R21 MH087903-02/MH/NIMH NIH HHS; R33 MH087903/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Neurotransmitter Agents; 0/Transcription Factor AP-2; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 2.1.1.28/Phenylethanolamine N-Methyltransferase; X4W3ENH1CV/Norepinephrine; YKH834O4BH/Epinephrine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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