title: Tafazzin knockdown interrupts cell cycle progression in cultured neonatal ventricular fibroblasts.
abstract: Mutation of the mitochondrial protein tafazzin causes dilated cardiomyopathy in Barth syndrome. Previous studies have shown that tafazzin knockdown promotes hypertrophy of neonatal cardiac myocytes. The current investigation was designed to show whether tafazzin knockdown affects cardiac fibroblast proliferation and collagen secretion, which contribute to fibrosis in dilated cardiomyopathy. In primary cultures of neonatal ventricular fibroblasts (NVFs) transduced with a tafazzin short hairpin RNA adenovirus, tafazzin knockdown increased production of reactive oxygen species and activation of mitogen-activated protein kinases and induced protein and DNA synthesis via cell cycle regulators. It also reduced intracellular ATP, activated AMPK, and caused multinucleation, hypertrophy, and enhanced collagen secretion. We concluded that tafazzin knockdown interrupts the NVF cell cycle and this in turn may contribute to fibrosis and dilated cardiomyopathy in Barth syndrome.
authors.affiliation: Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, Florida; and.
authors.forename: Quan
authors.initials: Q
authors.lastname: He
authors.forename: Miao
authors.initials: M
authors.lastname: Wang
authors.forename: Nicole
authors.initials: N
authors.lastname: Harris
authors.forename: Xianlin
authors.initials: X
authors.lastname: Han
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000217:Acyltransferases; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D056889:Barth Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002308:Cardiolipins / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004261:DNA Replication; D015536:Down-Regulation; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D055785:Gene Knockdown Techniques; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics; D014161:Transduction, Genetic; D014162:Transfection
chemical_list: D002308:Cardiolipins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D003094:Collagen; D000217:Acyltransferases; C544439:Tafazzin protein, rat; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: cardiolipin; cell cycle; mitogen-activated protein kinase; reactive oxygen species