title: Urotensin II induction of neonatal cardiomyocyte hypertrophy involves the CaMKII/PLN/SERCA 2a signaling pathway.
abstract: Although studies have shown that Urotensin II (UII) can induce cardiomyocyte hypertrophy and UII-induced cardiomyocyte hypertrophy model has been widely used for hypertrophy research, but its precise mechanism remains unknown. Recent researches have demonstrated that UII-induced cardiomyocyte hypertrophy has a relationship with the changes of intracellular Ca(2+) concentration. Therefore, the aim of this study was to investigate the mechanisms of cardiomyocyte hypertrophy induced by UII and to explore whether the calcium/calmodulin-dependent protein kinase II (CaMKII)-mediated up-regulating of phospholamban (PLN) Thr17-phosphorylation signaling pathway contributed to UII-induced cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were stimulated for 48h with UII. Cell size, protein/DNA contents and intracellular Ca(2+) were determined. Phosphorylated and total forms of CaMKII, PLN and the total amount of serco/endo-plasmic reticulum ATPases (SERCA 2a) were quantified by western blot. The responses of cardiomyocytes to UII were also evaluated after pretreatment with the CaMKII inhibitor, KN-93. These results showed that UII increased cell size, protein/DNA ratio and intracellular Ca(2+), consistent with a hypertrophic response. Furthermore, the phosphorylation of CaMKII and its downstream target PLN (Thr17), SERCA 2a levels were up-regulated by UII treatment. Conversely, treatment with KN-93 reversed all those effects of UII. Taken together, the results suggest that UII can induce cardiomyocyte hypertrophy through CaMKII-mediated up-regulating of PLN Thr17-phosphorylation signaling pathway.
authors.affiliation: Department of Cardiology, The First Hospital of Shanxi Medical University, PR China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Cardiology, The First Hospital of Shanxi Medical University, PR China. Electronic address: biohanqinghua@sohu.com.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Cardiology, The First Hospital of Shanxi Medical University, PR China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cardiology, The First Hospital of Shanxi Medical University, PR China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Linfen People's Hospital, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Chu
authors.affiliation: Department of Cardiology, The First Hospital of Shanxi Medical University, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D014579:Urotensins / Q000633:toxicity*; D000099211:Phospholamban; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D002118:Calcium; D002135:Calcium-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013449:Sulfonamides; D014579:Urotensins; D000099211:Phospholamban; C072105:KN 93; D000096926:Benzenesulfonamides; C029677:urotensin II
keywords: CaMKII; Cardiomyocyte hypertrophy; PLN; SERCA 2a; UII