Urotensin II induction of neonatal cardiomyocyte hypertrophy involves the CaMKII/PLN/SERCA 2a signaling pathway
| Autor: | Jianrong Xu, Wenyuan Liu, Tingting Chu, Hong-Tao Shi, Qing-Hua Han, Li Zhao |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Benzylamines ATPase Urotensins Biology Muscle hypertrophy Sarcoplasmic Reticulum Calcium-Transporting ATPases Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Calcium-binding protein Ca2+/calmodulin-dependent protein kinase Internal medicine Genetics medicine Animals Myocytes Cardiac Phosphorylation Cells Cultured Cell Size Sulfonamides Calcium-Binding Proteins General Medicine Hypertrophy Phospholamban 030104 developmental biology Endocrinology chemistry Animals Newborn cardiovascular system biology.protein Calcium Signal transduction Urotensin-II Calcium-Calmodulin-Dependent Protein Kinase Type 2 Signal Transduction |
| Zdroj: | Gene. 583(1) |
| ISSN: | 1879-0038 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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