Mitochondria, responding to a wide variety of signals, including oxidative stress, are critical in regulating apoptosis that plays a key role in the pathogenesis of a variety of cardiovascular diseases. A number of mitochondrial proteins and pathways have been found to be involved in the mitochondrial dependent apoptosis mechanism, such as optic atrophy 1 (OPA1), sirtuin 3 (Sirt3), deacetylase enzyme and cAMP signal. In the present work we report a network among 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-dependent apoptosis. FRET analysis revealed a selective decrease of mitochondrial cAMP in response to t-BHP treatment. This was associated with a decrease of Sirt3 protein level and proteolytic processing 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 the protein kinase A (PKA), and protease inhibitors, evidences have been obtained that ROS-dependent apoptosis is associated with an alteration of mitochondrial cAMP/PKA signal that causes degradation/proteolysis of Sirt3 that, in turn, promotes acetylation and proteolytic processing of OPA1.
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|Titolo:||Mitochondrial cAMP prevents apoptosis modulating Sirt3 protein level and OPA1 processing in cardiac myoblast cells|
|Data di pubblicazione:||2017|
|Citazione:||Mitochondrial cAMP prevents apoptosis modulating Sirt3 protein level and OPA1 processing in cardiac myoblast cells / Signorile, Anna; Santeramo, Arcangela; Tamma, Grazia; Pellegrino, Tommaso; D'Oria, Susanna; Lattanzio, Paolo; De Rasmo, Domenico. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. - ISSN 0167-4889. - 1864:2(2017), pp. 355-366.|
|Appare nelle tipologie:||1.1 Articolo in rivista|