Abstract

Mitochondria, responding to a wide variety of signals, including oxidative stress, are criticalin regulating apoptosis that plays a key role in the pathogenesis of a variety of cardiovasculardiseases. A number of mitochondrial proteins and pathways have been found to be involvedin the mitochondrial dependent apoptosis mechanism, such as optic atrophy 1 (OPA1), sirtuin3 (Sirt3), deacetylase enzyme and cAMP signal. In the present work we report a networkamong OPA1, Sirt3 and cAMP in ROS-dependent apoptosis. Rat myoblastic H9c2 cell lines,were treated with tert-butyl hydroperoxide (t-BHP) to induce oxidative stress-dependentapoptosis. FRET analysis revealed a selective decrease of mitochondrial cAMP in response tot-BHP treatment. This was associated with a decrease of Sirt3 protein level and proteolyticprocessing of OPA1. Pretreatment of cells with permeant analogous of cAMP (8-Br-cAMP)protected the cell from apoptosis preventing all these events. Using H89, inhibitor of theprotein kinase A (PKA), and protease inhibitors, evidences have been obtained that ROSdependentapoptosis is associated with an alteration of mitochondrial cAMP/PKA signal thatcauses degradation/proteolysis of Sirt3 that, in turn, promotes acetylation and proteolyticprocessing of OPA1.

Autore Pugliese

• De Rasmo Domenico , Lattanzio Paolo

Tutti gli autori

• A. Signorile; A. Santeramo; G. Tamma; T. Pellegrino; S. D'Oria; P. Lattanzio; D. De Rasmo

Titolo volume/Rivista

Biochimica et biophysica acta. Molecular cell research

Anno di pubblicazione

2016

ISSN

0167-4889

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

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Numero di citazioni Scopus

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Ultimo Aggiornamento Citazioni

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Settori ERC

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Codici ASJC

Non Disponibile