| Transcriptional control of pacemaker channel genes HCN2 and HCN4 by Sp1 and implications in re-expression of these genes in hypertrophied myocytes. | |
| | |
MedLine Citation:
|
PMID: 19471099 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Cardiac hypertrophy is characterized by electrical remolding with increased risk of arrhythmogenesis. Enhanced abnormal automaticity of ventricular cells may contribute to hypertrophic arrhythmias. The pacemaker current I(f), carried by the hyperpolarization-activated channels encoded mainly by the HCN2 and HCN4 genes in the heart, plays an important role in rhythmogenesis. Their expressions reportedly increase in hypertrophic and failing hearts, contributing to arrhythmogenesis under these conditions. However, how their expressions are controlled remained unclear. We performed a study to characterize the regulatory elements and transcriptional control of HCN2 and HCN4 genes. We identified the transcription start sites by 5'RACE and core promoter regions of these genes using luciferase reporter assay, and revealed the ubiquitous Sp1 protein as a common transactivator of HCN2 and HCN4 genes. We further unraveled robust increases in HCN2/HCN4 transcripts and protein levels, using real-time RT-PCR and Western blot analyses, in a rat model of left ventricular hypertrophy and in angiotensin II-induced neonatal ventricular hypertrophy. The upregulation of HCN2 and HCN4 transcription was accompanied by pronounced elevations of Sp1 and silencing of Sp1 by siRNA prevented overexpression of HCN2/HCN4 in hypertrophic cardiomyocytes. Our data indicate that Sp1 drives HCN2/HCN4 transcription and determines the functional level of HCN2/HCN4 mRNAs, and upregulation of Sp1 underlie the abnormal re-expression of HCN2/HCN4 genes in hypertrophied myocytes. This study also provides the first evidence for the role of Sp1 in the reactivation of 'fetal' cardiac genes, HCN2 and HCN4, in ventricular myocytes, and thereby in the pathological electrical remodeling in hypertrophied myocytes. |
| | |
Authors:
|
Huixian Lin; Jiening Xiao; Xiaobin Luo; Guorong Chen; Zhiguo Wang |
Related Documents
:
|
10524219 - The human gene coding for hcn2, a pacemaker channel of the heart. 17599489 - Early gene expression profiles during intraoperative myocardial ischemia-reperfusion in... 23365759 - Androgen receptor-target genes in african american prostate cancer disparities. 19725949 - Hypoxic transcription gene profiles under the modulation of nitric oxide in nuclear run... 15381649 - Periostin as a novel factor responsible for ventricular dilation. 23583519 - Immediate early gene and neuropeptide expression following exposure to the predator odo... 16292549 - In vivo effects of decitabine in myelodysplasia and acute myeloid leukemia: review of c... 1087329 - Multiple h-2 linked immune response gene control of h-2 d-associated t-cell-mediated ly... 16157749 - Association between tau h2 haplotype and age at onset in frontotemporal dementia. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-05-06 |
Journal Detail:
|
Title: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology Volume: 23 ISSN: 1421-9778 ISO Abbreviation: Cell. Physiol. Biochem. Publication Date: 2009 |
Date Detail:
|
Created Date: 2009-05-27 Completed Date: 2009-08-04 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9113221 Medline TA: Cell Physiol Biochem Country: Switzerland |
Other Details:
|
Languages: eng Pagination: 317-26 Citation Subset: IM |
Copyright Information:
|
Copyright 2009 S. Karger AG, Basel. |
Affiliation:
|
Research Center, Montreal Heart Institute, Montreal, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Angiotensin II
/
metabolism,
pharmacology Animals Base Sequence Cell Line Cyclic Nucleotide-Gated Cation Channels / genetics*, metabolism Humans Hypertrophy, Left Ventricular / genetics*, metabolism, pathology Immunoglobulins / genetics, metabolism* Ion Channels / genetics*, metabolism Molecular Sequence Data Muscle Proteins / genetics*, metabolism Myocytes, Cardiac / metabolism* Potassium Channels / genetics*, metabolism Promoter Regions, Genetic RNA, Messenger / metabolism RNA, Small Interfering / metabolism Rats Transcription, Genetic Up-Regulation |
| Chemical | |
Reg. No./Substance:
|
0/Cyclic Nucleotide-Gated Cation Channels; 0/HCN2 potassium channel; 0/HCN4 protein, human; 0/HCN4 protein, rat; 0/Immunoglobulins; 0/Ion Channels; 0/Muscle Proteins; 0/Potassium Channels; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/SP1 antigen; 11128-99-7/Angiotensin II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Ionic mechanisms underlying action potential prolongation by focal cerebral ischemia in rat ventricu...
Next Document: Crucial role of interleukin-6 in the development of norepinephrine-induced left ventricular remodeli...