Crola, Catherine (2015) Crosstalk between CaMKII and ERK in the regulation of cardiac hypertrophy. [Tesi di dottorato]

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: Crosstalk between CaMKII and ERK in the regulation of cardiac hypertrophy
Autori:
AutoreEmail
Crola, Catherinekalesch@hotmail.it
Data: 31 Marzo 2015
Numero di pagine: 33
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 27
Coordinatore del Corso di dottorato:
nomeemail
Avvedimento, Vittorio Enricoavvedim@unina.it
Tutor:
nomeemail
Illario, Maddalena[non definito]
Data: 31 Marzo 2015
Numero di pagine: 33
Parole chiave: Cardiac Hypertrophy; CaMKII
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Aree tematiche (7° programma Quadro): SALUTE e TUTELA DEL CONSUMATORE > Biotecnologie, strumenti e tecnologie generiche per la salute umana
Depositato il: 09 Apr 2015 12:09
Ultima modifica: 07 Mag 2016 01:00
URI: http://www.fedoa.unina.it/id/eprint/10400
DOI: 10.6092/UNINA/FEDOA/10400

Abstract

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 to develop cardiac hypertrophy 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 wit 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.

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