Document Detail


Angiotensin II and the JNK pathway mediate urotensin II expression in response to hypoxia in rat cardiomyocytes.
MedLine Citation:
PMID:  24481965     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Cardiomyocyte hypoxia causes cardiac hypertrophy through cardiac-restricted gene expression. Urotensin II (UII) cooperates with activating protein 1 (AP1) to regulate cardiomyocyte growth in response to myocardial injuries. Angiotensin II (AngII) stimulates UII expression, reactive oxygen species (ROS) production, and cardiac hypertrophy. This study aimed to evaluate the expression of UII, ROS, and AngII as well as their genetic transcription after hypoxia treatment in neonatal cardiomyocytes. Cultured neonatal rat cardiomyocytes were subjected to hypoxia for different time periods. UII (Uts2) protein levels increased after 2.5% hypoxia for 4 h with earlier expression of AngII and ROS. Both hypoxia and exogenously added AngII or Dp44mT under normoxia stimulated UII expression, whereas AngII receptor blockers, JNK inhibitors (SP600125), JNK siRNA, or N-acetyl-l-cysteine (NAC) suppressed UII expression. The gel shift assay indicated that hypoxia induced an increase in DNA-protein binding between UII and AP1. The luciferase assay confirmed an increase in transcription activity of AP1 to the UII promoter under hypoxia. After hypoxia, an increase in (3)H-proline incorporation in the cardiomyocytes and expression of myosin heavy chain protein, indicative of cardiomyocyte hypertrophy, were observed. In addition, hypoxia increased collagen I expression, which was inhibited by SP600125, NAC, and UII siRNA. In summary, hypoxia in cardiomyocytes increases UII and collagen I expression through the induction of AngII, ROS, and the JNK pathway causing cardiomyocyte hypertrophy and fibrosis.
Authors:
Chiung-Zuan Chiu; Bao-Wei Wang; Kou-Gi Shyu
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Publication Detail:
Type:  Journal Article     Date:  2014-01-30
Journal Detail:
Title:  The Journal of endocrinology     Volume:  220     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2014  
Date Detail:
Created Date:  2014-01-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  233-46     Citation Subset:  IM    
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