Document Detail


The defects in development and apoptosis of cardiomyocytes in mice lacking the transcriptional factor Pax-8.
MedLine Citation:
PMID:  20851479     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Cardiac-specific deletion of ALK3 is lethal in mid-gestation with ventricular septum malformations (VSM). This study was designed to define the Pax-8's role in heart development and cardiomyocyte apoptosis.
METHODS: Pathologic changes in the hearts of Pax-8 or ALK3 knockout and wild type control mice were determined by light and electron microscopy. Analysis of cardiomyocyte apoptosis was performed by TUNEL. The effect of Pax-8 gene deficiency on caspase-3 activity was examined after transfecting Pax-8 siRNA into cultured myoblast cell line.
RESULTS: Mice with ALK3 or Pax-8 gene knockout but not wild type control animals showed the development of VSM. Increased cardiomyocyte apoptosis was found in homozygotes. Echocardiography showed that Pax-8 homozygote mice developed malfunction of the heart. Furthermore, the caspase-3 activity was significantly higher in the cells treated with Pax-8 siRNA as compared to those treated with negative control siRNA in H9C2 (2-1) cell line.
CONCLUSIONS: The Pax-8 gene may play a crucial role in heart development and regulating cardiocyte apoptosis. Knockout of Pax-8 may exert a similar effect on myocardial morphology and apoptosis as those seen in ALK3 knockouts. Furthermore, the ventricular septum malformations could be partially attributed to accelerated cardiomyocyte apoptosis.
Authors:
Deye Yang; Dandan Lai; Xiaoyan Huang; Xiangxiang Shi; Zhan Gao; Fang Huang; Xi Zhou; Yong-Jian Geng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-20
Journal Detail:
Title:  International journal of cardiology     Volume:  154     ISSN:  1874-1754     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-05     Completed Date:  2012-08-13     Revised Date:  2012-11-09    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  43-51     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, PR China. Deyeyang203@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / genetics*
Bone Morphogenetic Protein Receptors, Type I / deficiency,  genetics
Cells, Cultured
Mice
Myocytes, Cardiac / cytology*
Paired Box Transcription Factors / deficiency,  genetics*
Chemical
Reg. No./Substance:
0/Paired Box Transcription Factors; 0/Pax8 protein, mouse; EC 2.7.11.30/Bmpr1a protein, mouse; EC 2.7.11.30/Bone Morphogenetic Protein Receptors, Type I

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