Cytochrome c oxidase is essential for copper-induced regression of cardiomyocyte hypertrophy

Xiao Zuo, Huiqi Xie, Daoyin Dong, Nenggang Jiang, Hongming Zhu, Y. James Kang

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Previous studies have shown that both copper (Cu) and vascular endothelial growth factor (VEGF) reduce the size of hypertrophic cardiomyocytes, but the Cu-induced regression is VEGF dependent. Studies in vivo have shown that hypertrophic cardiomyopathy is associated with a depression in cytochrome c oxidase (COX) activity, which could be involved in VEGF-mediated cellular function. The present study was undertaken to test the hypothesis that COX is a determinant factor in Cu-induced regression of cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were treated with phenylepherine (PE) at a final concentration of l00 μM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cells were then treated with Cu sulfate at a final concentration of 5 μM in cultures for 24 h with a concomitant presence of PE to examine the effect of Cu on the regression of cardiomyocyte hypertrophy. Cell size changes were determined by flow cytometry, protein content, and molecular markers. Gene silencing was applied to study the effect of COX activity change on the regression of cardiomyocyte hypertrophy. PE treatment decreased COX activity in hypertrophic cardiomyocytes, and Cu addition restored the activity along with the regression of cell hypertrophy. Gene silencing using siRNA targeting COX-I significantly inhibited COX activity and blocked the Cu-induced regression of cell hypertrophy. VEGF alone also restored COX activity; but under the condition of COX inhibition by gene silencing, VEGF-induced regression of cell hypertrophy was suppressed. This study demonstrates that both Cu and VEGF can restore COX activity that is depressed in hypertrophic cardiomyocytes, and COX plays a determinant role in both Cu- and VEGF-induced regression of cardiomyocyte hypertrophy.

Original languageEnglish (US)
Pages (from-to)208-215
Number of pages8
JournalCardiovascular Toxicology
Issue number3
StatePublished - Sep 2010


  • Cardiomyocytes
  • Cell size
  • Copper
  • Cytochrome c oxidase
  • VEGF

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Molecular Biology
  • Toxicology


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