Overexpression of ankyrin repeat domain 1 enhances cardiomyocyte apoptosis by promoting p53 activation and mitochondrial dysfunction in rodents

Shen, Liang; Chen, Ci; Xuan, Wei; Li, Xixian; Luo, Guangjin; Zhang, Jingwen; Bin, Jianping; Huang, Xiaobo; Cao, Shiping; Li, Guofeng; Liao, Yulin

doi:10.1042/cs20140586

Cited by 38 publications

(25 citation statements)

References 36 publications

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“…Overexpression of Ankrd1 (Ankyrin repeat domain 1) has been shown to enhance apoptosis 68 through the p53 pathway. Gdf15 (Growth Differentiation factor 15) is a member of the TGF-β superfamily and is widely distributed in mammalian tissues.…”

Section: Discussionmentioning

confidence: 99%

Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome

Lingappan

Maity

Jiang

et al. 2017

Sci Rep

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Hyperoxia contributes to lung injury in experimental animals and diseases such as acute respiratory distress syndrome in humans. Cytochrome P450 (CYP)1A enzymes are protective against hyperoxic lung injury (HLI). The molecular pathways and differences in gene expression that modulate these protective effects remain largely unknown. Our objective was to characterize genotype specific differences in the transcriptome and proteome of acute hyperoxic lung injury using the omics platforms: microarray and Reverse Phase Proteomic Array. Wild type (WT), Cyp1a1−/− and Cyp1a2−/− (8–10 wk, C57BL/6J background) mice were exposed to hyperoxia (FiO2 > 0.95) for 48 hours. Comparison of transcriptome changes in hyperoxia-exposed animals (WT versus knock-out) identified 171 genes unique to Cyp1a1−/− and 119 unique to Cyp1a2−/− mice. Gene Set Enrichment Analysis revealed pathways including apoptosis, DNA repair and early estrogen response that were differentially regulated between WT, Cyp1a1−/− and Cyp1a2−/− mice. Candidate genes from these pathways were validated at the mRNA and protein level. Quantification of oxidative DNA adducts with 32P-postlabeling also revealed genotype specific differences. These findings provide novel insights into mechanisms behind the differences in susceptibility of Cyp1a1−/− and Cyp1a2−/− mice to HLI and suggest novel pathways that need to be investigated as possible therapeutic targets for acute lung injury.

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Section: Discussionmentioning

confidence: 99%

Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome

Lingappan

Maity

Jiang

et al. 2017

Sci Rep

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“…In addition, a new study showed that ANKRD1 acts as a co-factor of the transcription factor GATA binding protein 4 (GATA-4) to induce anti-apoptosis Bcl2 gene expression in in vitro hypoxia/reoxygenation and in vivo ischemic/reperfusion experimental models, lending further support to the role of ANKRD1 as an anti-apoptotic factor [ 30 ]. Conversely, in a recent report by Shen and colleagues, overexpression of ANKRD1 led to an increase in cardiomyocyte apoptosis when hearts were stimulated with either angiotensin II or challenged by pressure overload, indicating that ANKRD1 could also have pro-apoptotic properties [ 64 ]. It is worth noting that ANKRD1 has also been linked to an increase in apoptotic cell death in human hepatoma cells [ 65 ].…”

Section: Pathological Cardiac Functions Of Ankrd1mentioning

confidence: 99%

Ankyrin Repeat Domain 1 Protein: A Functionally Pleiotropic Protein with Cardiac Biomarker Potential

Ling

Chen

Wang

et al. 2017

IJMS

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The ankyrin repeat domain 1 (ANKRD1) protein is a cardiac-specific stress-response protein that is part of the muscle ankyrin repeat protein family. ANKRD1 is functionally pleiotropic, playing pivotal roles in transcriptional regulation, sarcomere assembly and mechano-sensing in the heart. Importantly, cardiac ANKRD1 has been shown to be highly induced in various cardiomyopathies and in heart failure, although it is still unclear what impact this may have on the pathophysiology of heart failure. This review aims at highlighting the known properties, functions and regulation of ANKRD1, with focus on the underlying mechanisms that may be involved. The current views on the actions of ANKRD1 in cardiovascular disease and its utility as a candidate cardiac biomarker with diagnostic and/or prognostic potential are also discussed. More studies of ANKRD1 are warranted to obtain deeper functional insights into this molecule to allow assessment of its potential clinical applications as a diagnostic or prognostic marker and/or as a possible therapeutic target.

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“…Mammalian cells have ANK proteins that either induce or inhibit apoptosis. Cellular cardiac ankyrin repeat protein Ankrd1/CARP (ASPP1 and ASPP2) promotes apoptosis via interactions with cellular p53 (77,78). Murine nucling, an ortholog of the human uveal autoantigen with coiled-coil domains and ankyrin repeats (UACA) protein, associates with and promotes apoptosome nuclear translocation to further promote stressinduced apoptosis (79).…”

Section: Discussionmentioning

confidence: 99%

Vaccinia Virus Encodes a Novel Inhibitor of Apoptosis That Associates with the Apoptosome

Ryerson

Richards

Kvansakul

et al. 2017

J Virol

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Apoptosis is an important antiviral host defense mechanism. Here we report the identification of a novel apoptosis inhibitor encoded by the vaccinia virus (VACV) gene. is absent in the attenuated modified vaccinia virus Ankara (MVA) strain of VACV, a strain that stimulates apoptosis in several types of immune cells. M1 expression increased the viability of MVA-infected THP-1 and Jurkat cells and reduced several biochemical hallmarks of apoptosis, such as PARP-1 and procaspase-3 cleavage. Furthermore, ectopic expression decreased staurosporine-induced (intrinsic) apoptosis in HeLa cells. We then identified the molecular basis for M1 inhibitory function. M1 allowed mitochondrial depolarization but blocked procaspase-9 processing, suggesting that M1 targeted the apoptosome. In support of this model, we found that M1 promoted survival in overexpressing human Apaf-1 and procaspase-9, critical components of the apoptosome, or overexpressing only conformationally active caspase-9. In mammalian cells, M1 coimmunoprecipitated with Apaf-1-procaspase-9 complexes. The current model is that M1 associates with and allows the formation of the apoptosome but prevents apoptotic functions of the apoptosome. The M1 protein features 14 predicted ankyrin (ANK) repeat domains, and M1 is the first ANK-containing protein reported to use this inhibitory strategy. Since ANK-containing proteins are encoded by many large DNA viruses and found in all domains of life, studies of M1 may lead to a better understanding of the roles of ANK proteins in virus-host interactions. Apoptosis selectively eliminates dangerous cells such as virus-infected cells. Poxviruses express apoptosis antagonists to neutralize this antiviral host defense. The vaccinia virus (VACV) M1 ankyrin (ANK) protein, a protein with no previously ascribed function, inhibits apoptosis. M1 interacts with the apoptosome and prevents procaspase-9 processing as well as downstream procaspase-3 cleavage in several cell types and under multiple conditions. M1 is the first poxviral protein reported to associate with and prevent the function of the apoptosome, giving a more detailed picture of the threats VACV encounters during infection. Dysregulation of apoptosis is associated with several human diseases. One potential treatment of apoptosis-related diseases is through the use of designed ANK repeat proteins (DARPins), similar to M1, as caspase inhibitors. Thus, the study of the novel antiapoptosis effects of M1 via apoptosome association will be helpful for understanding how to control apoptosis using either natural or synthetic molecules.

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Overexpression of ankyrin repeat domain 1 enhances cardiomyocyte apoptosis by promoting p53 activation and mitochondrial dysfunction in rodents

Cited by 38 publications

References 36 publications

Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome

Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome

Ankyrin Repeat Domain 1 Protein: A Functionally Pleiotropic Protein with Cardiac Biomarker Potential

Vaccinia Virus Encodes a Novel Inhibitor of Apoptosis That Associates with the Apoptosome

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