Targeting the CaMKII/ERK Interaction in the Heart Prevents Cardiac Hypertrophy(345 views) Cipolletta E, Rusciano MR, Maione AS, Santulli G, Sorriento D, Del Giudice C, Ciccarelli M, Franco A, Crola C, Campiglia P, Sala M, Gomez-Monterrey I, De Luca N, Trimarco B, Iaccarino G, Illario M
Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking), 2015 Jun 25; 10(6): e0130477-e0130477.
Keywords: Camkii, Erk, Interaction, Cardiac Hypertrophy, Animals
, Butadienes Administration, Dosage
, Calcium-Calmodulin-Dependent Protein Kinase Type 2 Antagonists, Inhibitors Biosynthesis Metabolism
, Cardiomegaly Genetics Metabolism Pathology
, Gene Expression Regulation Drug Effects
, Heart Drug Effects Growth, Development
, Humans
, Mitogen-Activated Protein Kinase 3 Antagonists, Myoblasts, Cardiac Drug Effects Metabolism
, Nitriles Administration, Phenylephrine Metabolism
, Phosphorylation,
Affiliations: *** IBB - CNR ***
1Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.
2Department of Translational and Medical Sciences, Federico II University, Naples, Italy.
3Columbia University Medical Center, College of Physicians & Surgeons, New York Presbyterian Hospital-Manhattan, New York, NY, United States of America.
4Institute of Biostructure and Bioimaging (IBB) of Italian National Research Council (CNR), Naples, Italy.
5Department of Advanced Biomedical Science, Federico II University, Naples, Italy.
6Department of Pharmacy, University of Salerno, Fisciano, Italy.
7Department of Pharmacy, Federico II University, Naples, Italy.
Department of Medicine and Surgery, University of Salerno, Baronissi (SA), Italy.
Department of Translational and Medical Sciences, Federico II University, Naples, Italy.
Columbia University Medical Center, College of Physicians & Surgeons, New York Presbyterian Hospital-Manhattan, New York, NY, United States of America.
Institute of Biostructure and Bioimaging (IBB) of Italian National Research Council (CNR), Naples, Italy.
Department of Advanced Biomedical Science, Federico II University, Naples, Italy.
Department of Pharmacy, University of Salerno, Fisciano, Italy.
References: Not available.
Targeting the CaMKII/ERK Interaction in the Heart Prevents Cardiac Hypertrophy
AIMS: Activation of Ca2+/Calmodulin protein kinase II (CaMKII) is an important step in signaling of cardiac hypertrophy. The molecular mechanisms by which CaMKII integrates with other pathways in the heart are incompletely understood. We hypothesize that CaMKII association with extracellular regulated kinase (ERK), promotes cardiac hypertrophy through ERK nuclear localization. METHODS AND RESULTS: In H9C2 cardiomyoblasts, the selective CaMKII peptide inhibitor AntCaNtide, its penetratin conjugated minimal inhibitory sequence analog tat-CN17β, and the MEK/ERK inhibitor UO126 all reduce phenylephrine (PE)-mediated ERK and CaMKII activation and their interaction. Moreover, AntCaNtide or tat-CN17β pretreatment prevented PE induced CaMKII and ERK nuclear accumulation in H9C2s and reduced the hypertrophy responses. To determine the role of CaMKII in cardiac hypertrophy in vivo, spontaneously hypertensive rats were subjected to intramyocardial injections of AntCaNtide or tat-CN17β. Left ventricular hypertrophy was evaluated weekly for 3 weeks by cardiac ultrasounds. We observed that the treatment with CaMKII inhibitors induced similar but significant reduction of cardiac size, left ventricular mass, and thickness of cardiac wall. The treatment with CaMKII inhibitors caused a significant reduction of CaMKII and ERK phosphorylation levels and their nuclear localization in the heart. CONCLUSION: These results indicate that CaMKII and ERK interact to promote activation in hypertrophy; the inhibition of CaMKII-ERK interaction offers a novel therapeutic approach to limit cardiac hypertrophy.
Targeting the CaMKII/ERK Interaction in the Heart Prevents Cardiac Hypertrophy
Vitiello M, Finamore E, Falanga A, Raieta K, Cantisani M, Galdiero F, Pedone C, Galdiero M, Galdiero S * Fusion in Coq(578 views) Lecture Notes In Computer Science (ISSN: 0302-9743, 0302-974335404636319783540463634, 0302-974335402975459783540297543), 2001; 2178LNCS: 583-596. Impact Factor:0.415 ViewExport to BibTeXExport to EndNote