Correction: Akap1 Deficiency Promotes Mitochondrial Aberrations and Exacerbates Cardiac Injury Following Permanent Coronary Ligation via Enhanced Mitophagy and Apoptosis

Schiattarella, Gabriele Giacomo; Cattaneo, Fabio; Pironti, Gianluigi; Magliulo, Fabio; Colella, Giuseppe; Pirozzi, Marinella; Polishchuk, Roman; Borzacchiello, Domenica; Paolillo, Roberta; Oliveti, Marco; Boccella, Nicola; Avvedimento, Marisa; Sepe, Maria; Gargiulo, Giuseppe; Lombardi, Assunta; Busiello, Rosa Anna; Trimarco, Bruno; Esposito, Giovanni; Feliciello, Antonio; Perrino, Cinzia

doi:10.1371/journal.pone.0158934

Cited by 17 publications

(20 citation statements)

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“…Degradation of AKAP121 is mediated, in part, by the E3 ubiquitin ligase seven in absentia homolog 2 ( Siah2 ; Carlucci et al, 2008a ). Previous studies in our laboratory and others have also shown that AKAP121 degradation upon ischemia is reduced in Siah2 knockout mice ( Siah2 -/- ; Kim et al, 2011 ; Schiattarella et al, 2016 ), and that Siah2 deletion reduces cardiac susceptibility to ischemia due to loss of Akap1 ( Schiattarella et al, 2016 ). Although the potential role of AKAP121 in the hypertrophic growth of cardiomyocytes has been suggested by in vitro studies ( Abrenica et al, 2009 ), basal cardiac mass, structure, and function of Akap1 -/- mice were not significantly different compared to their wt littermates.…”

Section: Introductionsupporting

confidence: 51%

“…All experiments involving animals in this study were conformed to the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication 8th edition, update 2011), and were approved by the animal welfare regulation of University of Naples Federico II, Naples, Italy, and by the Ministry of Health, Italy. Akap 1 knockout mice ( Akap 1 -/- , C57BL/6 background) and Akap1 heterozygous mice ( Akap +/- , C57BL/6 background) were kindly donated by McKnight G. S. and have been previously described ( Newhall et al, 2006 ; Schiattarella et al, 2016 ). Siah2 knockout mice ( Siah2 -/- , C57BL/6 background) were kindly donated by Bowtell D. Wild-type ( wt , C57BL/6 background) Akap 1 +/- and Akap 1 -/- mice of either gender (8–9 weeks old) were included in the study and maintained under identical conditions of temperature (21 ± 1°C), humidity (60 ± 5%), and light/dark cycle, and had free access to normal mouse chow.…”

Section: Methodsmentioning

confidence: 99%

“…LVH and ultimately HF are characterized by mitochondrial dysfunction leading to reduced ATP production and increased generation of mitochondrial reactive oxygen species (ROS; Torrealba et al, 2017 ). A sub-family of AKAPs deriving from the alternative splicing of the Akap1 gene amplifies signals to mitochondria (mitoAKAPs), and has been shown to be critical under several pathological conditions ( Carlucci et al, 2008a ; Perrino et al, 2010 ; Scorziello et al, 2013 ; Schiattarella et al, 2016 ). We have previously demonstrated that the absence of Akap1 exacerbates cardiac injury following myocardial infarction in mice, promoting mitochondrial dysfunction, enhancing ROS production and infarct size, and ultimately reducing survival ( Schiattarella et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…A sub-family of AKAPs deriving from the alternative splicing of the Akap1 gene amplifies signals to mitochondria (mitoAKAPs), and has been shown to be critical under several pathological conditions ( Carlucci et al, 2008a ; Perrino et al, 2010 ; Scorziello et al, 2013 ; Schiattarella et al, 2016 ). We have previously demonstrated that the absence of Akap1 exacerbates cardiac injury following myocardial infarction in mice, promoting mitochondrial dysfunction, enhancing ROS production and infarct size, and ultimately reducing survival ( Schiattarella et al, 2016 ). Using a rat model of LVH, we have shown that degradation of AKAP121, the most abundant Akap1 product in muscle cells, occurs early in response to pressure overload, and is associated with impaired mitochondrial function and reduced cell survival ( Perrino et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

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Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

et al. 2018

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Left ventricular hypertrophy (LVH) is a major contributor to the development of heart failure (HF). Alterations in cyclic adenosine monophosphate (cAMP)-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA) anchor proteins (AKAPs), tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs) promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 (Akap1-/-), Akap1 heterozygous (Akap1+/-), and their wild-type (wt) littermates underwent transverse aortic constriction (TAC) or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1-/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 (Siah2) knockout mice (Siah2-/-). Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

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Section: Introductionsupporting

confidence: 51%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

et al. 2018

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“…This provides a fine feed-back mechanism of signal attenuation in the presence of limiting amounts of oxygen (Carlucci et al, 2008b). In neurons and in cardiomyocytes, prolonged downregulation of AKAP1 induces oxidative stress and mitochondrial fragmentation, that eventually leads to mitophagy and cell death (Schiattarella et al, 2016(Schiattarella et al, , 2018. On the contrary, forced relocalization of PKA to mitochondria by AKAP1 reduces mitochondrial stress and prevents oxidative damage and death of cultured neurons isolated from PINK1 knockout mice or subjected to RNAi mediated silencing (Dagda et al, 2011).…”

Section: Potential Therapeutic Strategies For Pdmentioning

confidence: 99%

Mitochondrial Homeostasis and Signaling in Parkinson’s Disease

Scorziello

Borzacchiello

Sisalli

et al. 2020

Front. Aging Neurosci.

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The loss of dopaminergic (DA) neurons in the substantia nigra leads to a progressive, long-term decline of movement and other non-motor deficits. The symptoms of Parkinson's disease (PD) often appear later in the course of the disease, when most of the functional dopaminergic neurons have been lost. The late onset of the disease, the severity of the illness, and its impact on the global health system demand earlier diagnosis and better targeted therapy. PD etiology and pathogenesis are largely unknown. There are mutations in genes that have been linked to PD and, from these complex phenotypes, mitochondrial dysfunction emerged as central in the pathogenesis and evolution of PD. In fact, several PD-associated genes negatively impact on mitochondria physiology, supporting the notion that dysregulation of mitochondrial signaling and homeostasis is pathogenically relevant. Derangement of mitochondrial homeostatic controls can lead to oxidative stress and neuronal cell death. Restoring deranged signaling cascades to and from mitochondria in PD neurons may then represent a viable opportunity to reset energy metabolism and delay the death of dopaminergic neurons. Here, we will highlight the relevance of dysfunctional mitochondrial homeostasis and signaling in PD, the molecular mechanisms involved, and potential therapeutic approaches to restore mitochondrial activities in damaged neurons.

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Knockdown of A‐kinase anchor protein 4 inhibits hypoxia‐induced epithelial‐to‐mesenchymal transition via suppression of the Wnt/β‐catenin pathway in human gastric cancer cells

Tang

et al. 2018

J of Cellular Biochemistry

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Hypoxia induces epithelial-mesenchymal transition (EMT) in tumorigenesis. A-kinase anchor protein 4 (AKAP4) is a member of AKAPs family and plays a critical role in tumorigenesis. However, the biological role of AKAP4 in gastric cancer remains unknown. Thus, we investigated the effect of AKAP4 on EMT in human gastric cancer cells under hypoxic conditions. Our results showed that AKAP4 expression was significantly upregulated in human gastric cancer cell lines. In addition, silenced expression of hypoxia-inducible factor-1α markedly suppressed AKAP4 expression in gastric cancer cells under hypoxia. Furthermore, knockdown of AKAP4 significantly prevented hypoxia-induced migration, invasion, and EMT process in gastric cancer cells. Mechanistically, knockdown of AKAP4 prevented the activation of the Wnt/β-catenin pathway in gastric cancer cells under hypoxia condition. These findings indicate that knockdown of AKAP4 inhibits hypoxia-induced EMT in human gastric cancer cells, at least in part, via inactivation of the Wnt/β-catenin signaling pathway. It is, therefore, AKAP4 may be a potential therapeutic target for the treatment of gastric cancer.

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Correction: Akap1 Deficiency Promotes Mitochondrial Aberrations and Exacerbates Cardiac Injury Following Permanent Coronary Ligation via Enhanced Mitophagy and Apoptosis

Cited by 17 publications

References 1 publication

Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

Mitochondrial Homeostasis and Signaling in Parkinson’s Disease

Knockdown of A‐kinase anchor protein 4 inhibits hypoxia‐induced epithelial‐to‐mesenchymal transition via suppression of the Wnt/β‐catenin pathway in human gastric cancer cells

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