Angiotensin II and the JNK pathway mediate urotensin II expression in response to hypoxia in rat cardiomyocytes

Chiung Zuan Chiu, Bao Wei Wang, Kou Gi Shyu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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 3H-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.

Original languageEnglish
Pages (from-to)233-246
Number of pages14
JournalJournal of Endocrinology
Volume220
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

MAP Kinase Signaling System
Cardiac Myocytes
Angiotensin II
Reactive Oxygen Species
Acetylcysteine
Cardiomegaly
Proteins
Hypertrophy
Small Interfering RNA
Collagen
Genetic Transcription
urotensin II
Hypoxia
Myosin Heavy Chains
Angiotensin Receptor Antagonists
DNA-Binding Proteins
Luciferases
Proline
Fibrosis
Gels

Keywords

  • Cardiac hypertrophy
  • Hypoxia
  • Reactive oxygen species
  • Transcriptional activity

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Angiotensin II and the JNK pathway mediate urotensin II expression in response to hypoxia in rat cardiomyocytes. / Chiu, Chiung Zuan; Wang, Bao Wei; Shyu, Kou Gi.

In: Journal of Endocrinology, Vol. 220, No. 3, 03.2014, p. 233-246.

Research output: Contribution to journalArticle

Chiu, Chiung Zuan ; Wang, Bao Wei ; Shyu, Kou Gi. / Angiotensin II and the JNK pathway mediate urotensin II expression in response to hypoxia in rat cardiomyocytes. In: Journal of Endocrinology. 2014 ; Vol. 220, No. 3. pp. 233-246.
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