Tafazzin knockdown causes hypertrophy of neonatal ventricular myocytes.

Abstract

Mutation of the mitochondrial protein tafazzin causes dilated cardiomyopathy in Barth syndrome. We employed an adenovirus as a vector to transfer tafazzin small hairpin RNA (shRNA) into neonatal ventricular myocytes (NVMs) to investigate the effects of tafazzin knockdown. The tafazzin shRNA adenovirus consistently knocked down tafazzin mRNA and lowered cardiolipin while significantly decreasing the production of ATP by the mitochondria. The phosphorylation of AMP-activated protein kinase and mitochondrial density were both increased in tafazzin knockdown NVMs compared with scrambled shRNA controls. When we tested whether tafazzin knockdown causes hypertrophy in vitro, we found that the surface area of NVMs infected with tafazzin shRNA adenovirus was significantly increased, as were the protein synthesis and expression of the hypertrophic marker gene, brain natriuretic peptide. Taken together, our data support the concept that a decreased tafazzin expression causes cardiomyocyte hypertrophy in vitro.

• Authors: Quan He
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 299 Issue 1 Pg. H210-6 (Jul 2010) ISSN: 1522-1539 [Electronic] United States
• PMID: 20348225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiolipins
• RNA, Messenger
• Transcription Factors
• Natriuretic Peptide, Brain
• Adenosine Triphosphate
• Acyltransferases
• Tafazzin protein, rat
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Acyltransferases
• Adenosine Triphosphate (metabolism)
• Adenoviridae (genetics)
• Animals
• Animals, Newborn
• Cardiolipins (metabolism)
• Cardiomegaly (genetics, metabolism, pathology)
• Cells, Cultured
• Energy Metabolism
• Gene Knockdown Techniques
• Genetic Vectors
• Heart Ventricles (metabolism, pathology)
• Mitochondria, Heart (metabolism)
• Myocytes, Cardiac (metabolism, pathology)
• Natriuretic Peptide, Brain (metabolism)
• Phosphorylation
• RNA Interference
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Transcription Factors (genetics, metabolism)
• Transfection