ArticleThe Journal of biological chemistry2013
Transcription factor Foxo3a prevents apoptosis by regulating calcium through the apoptosis repressor with caspase recruitment domain.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 62 citations in OpenAlex.
- VCAM-1/Ezrin axis antagonizes myocardial damage in ischemia-reperfusion injury.Cell death and differentiation · 2026Article
- Article
- Rosmarinic acid attenuated inflammation and apoptosis in folic acid-induced renal injury: Role of FoxO3/ NFκB pathway.Iranian journal of basic medical sciences · 2025Article
- Role of apoptosis repressor with caspase recruitment domain in human health and chronic diseases.Annals of medicine · 2024Review
- MicroRNAs-associated with FOXO3 in cellular senescence and other stress responses.Biogerontology · 2024Review
- CD38 Deficiency Alleviates Diabetic Cardiomyopathy by Coordinately Inhibiting Pyroptosis and Apoptosis.International journal of molecular sciences · 2023Article
- Article
- A double-edged sword: role of apoptosis repressor with caspase recruitment domain (ARC) in tumorigenesis and ischaemia/reperfusion (I/R) injury.Apoptosis : an international journal on programmed cell death · 2023Review
- The forkhead box O3 (FOXO3): a key player in the regulation of ischemia and reperfusion injury.Cellular and molecular life sciences : CMLS · 2023Review
- Mortality prediction in patients with hyperglycaemic crisis using explainable machine learning: a prospective, multicentre study based on tertiary hospitals.Diabetology & metabolic syndrome · 2023Article
- FOXO3a-dependent PARKIN negatively regulates cardiac hypertrophy by restoring mitophagy.Cell & bioscience · 2022Article
- Article
- Transcription Factors Involved in the Development and Prognosis of Cardiac Remodeling.Frontiers in pharmacology · 2022Review
- The impact of hyperglycaemic crisis episodes on long-term outcomes for inpatients presenting with acute organ injury: A prospective, multicentre follow-up study.Frontiers in endocrinology · 2022Article
- Construction of miRNA-mRNA network reveals crucial miRNAs and genes in acute myocardial infarction.Journal of biomedical research · 2021Article
- Role of apoptosis repressor with caspase recruitment domain (ARC) in cell death and cardiovascular disease.Apoptosis : an international journal on programmed cell death · 2021Review
- Transcriptomic Regulation of Muscle Mitochondria and Calcium Signaling by Insulin/IGF-1 Receptors Depends on FoxO Transcription Factors.Frontiers in physiology · 2021Article
- Role of apoptosis repressor with caspase recruitment domain (ARC) in cancer.Oncology letters · 2019Review
- Forkhead box O3 protects the heart against paraquat-induced aging-associated phenotypes by upregulating the expression of antioxidant enzymes.Aging cell · 2019Article
- DL-Propargylglycine protects against myocardial injury induced by chronic intermittent hypoxia through inhibition of endoplasmic reticulum stress.Sleep & breathing = Schlaf & Atmung · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Apoptosis can occur in the myocardium under a variety of pathological conditions, including myocardial infarction and heart failure. The forkhead family of transcription factor Foxo3a plays a pivotal role in apoptosis; however, its role in regulating cardiac apoptosis remains to be fully elucidated. We showed that enforced expression of Foxo3a inhibits cardiomyocyte apoptosis, whereas knockdown of endogenous Foxo3a sensitizes cardiomyocytes to undergo apoptosis. The apoptosis repressor with caspase recruitment domain (ARC) is a potent anti-apoptotic protein. Here, we demonstrate that it attenuates the release of calcium from the sarcoplasmic reticulum and inhibits calcium elevations in the cytoplasm and mitochondria provoked by oxidative stress in cardiomyocytes. Furthermore, Foxo3a is shown to maintain cytoplasmic and mitochondrial calcium homeostasis through ARC. We observed that Foxo3a knock-out mice exhibited enlarged myocardial infarction sizes upon ischemia/reperfusion, and ARC transgenic mice demonstrated reduced myocardial infarction and balanced calcium levels in mitochondria and sarcoplasmic reticulum. Moreover, we showed that Foxo3a activates ARC expression by directly binding to its promoter. This study reveals that Foxo3a maintains calcium homeostasis and inhibits cardiac apoptosis through trans-activation of the ARC promoter. These findings provided novel evidence that Foxo3a and ARC constitute an anti-apoptotic pathway that regulates calcium homeostasis in the heart.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.