title: Overexpression of PEP-19 suppresses angiotensin II-induced cardiomyocyte hypertrophy.
abstract: The precise molecular mechanisms leading to disturbance of Ca(2+)/calmodulin-dependent intracellular signalling in cardiac hypertrophy remains unclear. As an endogenous calmodulin regulator protein, the pathophysiology role of PEP-19 during cardiac hypertrophy was investigated in the present study. We here demonstrated that PEP-19 protein levels are significantly elevated in the aortic banding model in vivo and angiotensin II-induced cardiomyocyte hypertrophy in vitro. Consistent with inhibitory actions of PEP-19 on cardiomyocyte hypertrophy, induction of CaMKII and calcineurin activation as well as hypertrophy-related genes including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was significantly inhibited by PEP-19 transfection. Moreover, PEP-19 partially ameliorates angiotensin II-induced elevation of phospho-phospholamban (Thr-17) and sarcoplasmic reticulum Ca(2+) release in cardiomyocytes. Together, our results suggest that PEP-19 attenuates angiotensin II-induced cardiomyocyte hypertrophy via suppressing the disturbance of CaMKII and calcineurin signaling.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University of Technology, China.
authors.forename: Yang-yang
authors.initials: YY
authors.lastname: Xie
authors.forename: Meng-meng
authors.initials: MM
authors.lastname: Sun
authors.forename: Xue-fang
authors.initials: XF
authors.lastname: Lou
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.forename: Bo-ya
authors.initials: BY
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Ying-mei
authors.initials: YM
authors.lastname: Lu
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D015870:Gene Expression; D006984:Hypertrophy / Q000235:genetics; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D019703:Calcineurin; D002118:Calcium; D002135:Calcium-Binding Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins; D000099211:Phospholamban; C489090:Pcp4 protein, rat