Adenovirus-mediated overexpression of cardiac troponin I-interacting kinase promotes cardiomyocyte hypertrophy

Clin Exp Pharmacol Physiol. 2011 Apr;38(4):278-84. doi: 10.1111/j.1440-1681.2011.05499.x.

Abstract

1. Cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific kinase gene. Quantitative real-time reverse transcription polymerase chain reaction analysis showed a significant increase in TNNI3K mRNA expression in hypertrophic cardiomyocytes induced by endothelin-1 (ET-1). The aim of the present study was to investigate the effects of TNNI3K on neonate rat cardiomyocyte hypertrophy induced by ET-1. 2. Adenoviruses were amplified in 293A cells. To determine a reasonable adenovirus infection dose cardiomyocytes were infected with an adenovirus carrying human TNNI3K (Ad-TNNI3K) at varying multiplicity of infection (MOI) and the expression of TNNI3K was analysed by western blot. 3. Cardiomyocytes were infected with either a control adenovirus carrying green fluorescent protein (Ad-GFP) or Ad-TNNI3K. Compared with Ad-GFP, the Ad-TNNI3K induced an increase in sarcomere organization, cell surface area, (3) H-leucine incorporation and β-MHC re-expression. This type of hypertrophic phenomenon is similar to that observed in Ad-GFP-infected hypertrophic cardiomyocytes induced by ET-1. To determine the functional role of TNNI3K in ET-1-induced hypertrophic cardiomyocytes, the cells were infected with Ad-GFP or Ad-TNNI3K. Ad-TNNI3K induced an increase in sarcomere organization, cell surface area and (3) H-leucine incorporation compared with Ad-GFP. 4. These results suggest that TNNI3K overexpression induces cardiomyocytes hypertrophy and accelerates hypertrophy in hypertrophic cardiomyocytes. Therefore, TNNI3K might be an interesting target for the clinical treatment of hypertrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Cardiomegaly / enzymology*
  • Cells, Cultured
  • Endothelin-1 / pharmacology
  • Gene Expression / drug effects
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics
  • Humans
  • Leucine / metabolism
  • MAP Kinase Kinase Kinases / biosynthesis
  • MAP Kinase Kinase Kinases / genetics*
  • MAP Kinase Kinase Kinases / metabolism*
  • Myocytes, Cardiac / enzymology*
  • Protein Serine-Threonine Kinases
  • Rats
  • Rats, Sprague-Dawley
  • Sarcomeres / drug effects
  • Sarcomeres / enzymology
  • Ventricular Myosins / biosynthesis
  • Ventricular Myosins / genetics

Substances

  • Endothelin-1
  • Green Fluorescent Proteins
  • Protein Serine-Threonine Kinases
  • TNNI3K protein, human
  • MAP Kinase Kinase Kinases
  • Ventricular Myosins
  • Leucine