title: Caffeine induces cardiomyocyte hypertrophy via p300 and CaMKII pathways.
abstract: Caffeine is commonly utilized to trigger intracellular calcium in cardiomyocyte. It is well accepted that caffeine could induce cardiac arrhythmia, but it is not clear with regard of its impacts on the cardiac function. This article presents a recent study concerning the effects of caffeine on the cardiomyocyte hypertrophy and the associated signal pathway. The experimental results showed that the total protein contents, the surface area of cardiomyocyte and β-myosin heavy chain (β-MHC) expression increased in ventricular myocytes of neonatal Sprague-Dawley (SD) rats after 24h caffeine incubation. It is also observed that the basal intracellular calcium (Ca(2+)) level has increased, while the amplitude of Ca(2+) oscillation and Ca(2+) content have decreased in sarcoplasmic reticulum (SR). The caffeine-induced myocyte enhancer factor-2 (MEF2) expression and hypertrophy can be completely abolished by the inhibition of cardiac ryanodine receptor (RyR2), as well as KN93 and curcumin treatments. Meanwhile, the amplitude of Ca(2+) oscillation and the Ca(2+) content of SR in the completely-inhibited group have reached the physiological level. These results suggest that the caffeine-induced cardiomyocyte hypertrophy established the connection between Ca(2+) release from SR and cytosol that activates CaMKII and p300, which in turn enhances the expression of MEF2 that promotes 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, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
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, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
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, People's Republic of China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Wei
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, People's Republic of China.
authors.forename: Xingfeng
authors.initials: X
authors.lastname: Ma
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, People's Republic of China. Electronic address: zhangjb@mail.xjtu.edu.cn.
authors.forename: Jianbao
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002110:Caffeine / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D006984:Hypertrophy / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002110:Caffeine; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: CaMKII; Caffeine; Calcium; Hypertrophy; p300