کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9410571 | 1291266 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Short chain fatty acids regulate tyrosine hydroxylase gene expression through a cAMP-dependent signaling pathway
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کلمات کلیدی
VPAIP3inositol triphosphatePC12pKaPAGESCFAcyclic adenosine mono phosphateERKDDACATPPENKmRNATSAEMSACRECREBcAMP - cAMPmessenger RNA - RNA messengerElectrophoretic mobility shift assay - آزمون تحرک تحرک الکتروفورزShort chain fatty acids - اسیدهای چرب پایه کوتاهpolyacrylamide gel electrophoresis - الکتروفورز ژل پلی آکریل آمیدNeurotransmitters, Modulators, Transporters, and Receptors - انتقال دهنده های عصبی، مدولاتورها، حمل کننده ها و گیرنده هاButyrate - بوتیراتTrichostatin A - تریکوستاتین Atyrosine hydroxylase - تیروزین هیدروکسیلازpheochromocytoma cell line - خط سلول فئوکروموسیتوماTranscription - رونویسیSodium butyrate - سدیم butyrateextracellular signal regulated kinase - سیگنال خارج سلولی kinase را تنظیم می کندcAMP response element - عنصر پاسخ cAMPcAMP pathway - مسیر cAMPhistone deacetylase inhibitor - مهار کننده هیستون داسیدلازValproic acid - والپروات و والپروات سدیم یا والپروئیک اسیدcAMP response element binding protein - پروتئین اتصال دهنده عنصر پاسخ cAMPprotein kinase A - پروتئین کیناز Amitogen-activated protein kinase - پروتئین کیناز فعال با mitogenPreproenkephalin - پروپرانکفالینcatecholamines - کاتکول امینchloramphenicol acetyl transferase - کلرامفنیکول استیل ترانسفرازMAP kinase - کیناز MAP
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Multiple intracellular and extracellular regulatory factors affect transcription of the tyrosine hydroxylase (TH) gene encoding the rate-limiting enzyme in the biosynthesis of the neurotransmitters dopamine, norepinephrine and epinephrine. Short chain fatty acids like butyrate are known to alter TH gene expression, but the mechanism of action is unknown. In this report, transient transfection assays identified the proximal TH promoter to contain sufficient genetic information to confer butyrate responsiveness to a reporter gene. Deletion studies and gel shift analyses revealed that the promoter region spanning the cAMP response element is an absolute requirement for transcriptional activation by butyrate. The branched short chain fatty acid valproate is used for seizure control in humans. Significantly, it has a similar aliphatic structure to butyrate, and it was found to have similar effects on TH in PC12 cells. Site-directed mutagenesis indicated that the effects of both fatty acids were mediated through the canonical CRE. Butyrate treatment also resulted in CREB phosphorylation without changing CREB protein levels. The increased phosphorylation of CREB correlated with accumulation of TH mRNA. The adenylate cyclase inhibitor dideoxyadenosine blocked both CREB phosphorylation and accumulation of TH mRNA. The data are consistent with the conclusion that butyrate induces post-translational modifications of pre-existing CREB molecules in a cAMP/PKA-dependent manner to alter TH transcription. These results support the role of butyrate as a novel exogenous regulatory factor in TH gene expression. Our data delineate a molecular mechanism through which diet-derived environmental signals (e.g. butyrate) can modulate catecholaminergic systems by affecting TH gene transcription.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Brain Research - Volume 142, Issue 1, 7 December 2005, Pages 28-38
Journal: Molecular Brain Research - Volume 142, Issue 1, 7 December 2005, Pages 28-38
نویسندگان
Manuel DeCastro, Bistra B. Nankova, Parul Shah, Pranav Patel, Pradeep V. Mally, Ravi Mishra, Edmund F. La Gamma,