title: Effect of distinct sources of Ca(2+) on cardiac hypertrophy in cardiomyocytes.
abstract: It is believed that intracellular calcium (Ca(2+)) overload can cause the cardiac hypertrophy, but it is possible that the Ca(2+) entering the cytoplasm through distinct pathways will induce various effects on cardiomyocytes. The aim of the present study is to explore the effect of different sources of Ca(2+) on cardiomyocyte hypertrophy. The cardiomyocytes isolated from neonatal Sprague-Dawley rats were treated with three agents (ionomycin, caffeine and angiotensin II [Ang II]) that increased the intracellular Ca(2+) concentration via different pathways. Treatments with ionomycin, caffeine and Ang II for 24 h caused a significant increase in resting [Ca(2+)](i) by 108.0 ± 7.8%, 102.0 ± 6.9% and 59.8 ± 3.3%, respectively. Caffeine and Ang II increased the cell surface area of cardiomyocytes and the mRNA level of atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain, but ionomycin did not. Moreover, sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) activity and the amplitudes of the twitch [Ca(2+)](i) transients were reduced in the caffeine-treated group and Ang II-treated group. Furthermore, cardiomyocyte hypertrophy induced by caffeine was inhibited by cyclosporin A (CsA) and KN93, whereas cardiomyocyte hypertrophy induced by Ang II was inhibited by KN93, but not CsA. Our results show that cardiomyocyte hypertrophy is associated with SERCA2a activity, contractile performance and signaling pathways of CaMKII and/or calcineurin, whereas the Ca(2+) overload is not sufficient to cause the cardiomyocyte hypertrophy.
authors.affiliation: The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049,  China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.forename: Junqing
authors.initials: J
authors.lastname: Sun
authors.forename: Jinhong
authors.initials: J
authors.lastname: Wei
authors.forename: Lijun
authors.initials: L
authors.lastname: Sun
authors.forename: Jianbao
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019703:Calcineurin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium