title: Adenovirus-mediated overexpression of cardiac troponin I-interacting kinase promotes cardiomyocyte hypertrophy.
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.
authors.affiliation: Core laboratory, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Jue
authors.initials: J
authors.lastname: Ye
authors.forename: Rui-Xia
authors.initials: RX
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.forename: Na
authors.initials: N
authors.lastname: Shi
authors.forename: Yan-Wan
authors.initials: YW
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Xian-Min
authors.initials: XM
authors.lastname: Meng
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007930:Leucine / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000187:drug effects / Q000201:enzymology; D024723:Ventricular Myosins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019332:Endothelin-1; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; C481078:TNNI3K protein, human; D020930:MAP Kinase Kinase Kinases; D024723:Ventricular Myosins; D007930:Leucine