The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
The FOXO3a Transcription Factor Regulates Cardiac Myocyte Size Downstream of AKT Signaling
Open accessAbstract
Although signaling mechanisms inducing cardiac hypertrophy have been extensively studied, little is known about the mechanisms that reverse cardiac hypertrophy. Here, we describe the existence of a similar Akt/forkhead signaling axis in cardiac myocytes in vitro and in vivo, which is regulated by insulin, insulin-like growth factor (IGF), stretch, pressure overload, and angiotensin II stimulation. FOXO3a gene transfer prevented both IGF and stretch-induced hypertrophy in rat neonatal cardiac myocyte cultures in vitro. Transduction with FOXO3a also caused a significant reduction in cardiomyocyte size in mouse hearts in vivo. Akt/FOXO signaling regulated the expression of multiple atrophy-related genes "atrogenes," including the ubiquitin ligase atrogin-1 (MAFbx). In cardiac myocyte cultures, transduction with constitutively active Akt or treatment with IGF suppressed atrogin-1 mRNA expression, whereas transduction with FOXO3a stimulated its expression. FOXO3a transduction activated the atrogin-1 promoter in both cultured myocytes and mouse heart. Thus, in cardiomyocytes, as in skeletal muscle, FOXO3a activates an atrogene transcriptional program, which retards or prevents hypertrophy and is down-regulated by multiple physiological and pathological stimuli of myocyte growth.
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Cited by
The intersection between aging and cardiovascular disease
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FOXO transcription factors at the interface between longevity and tumor suppression
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Self-citationMolecular basis of physiological heart growth: fundamental concepts and new players
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Mitochondrial Sirtuin 3: New emerging biological function and therapeutic target
Zhang, J., Xiang, H., Liu, J., Chen, Y., He, R.-R., & Liu, B. (2020) · Theranostics · doi:10.7150/thno.45922 · Cited by 503
Metadata
- Authors
- Skurk, C., Izumiya, Y., Maatz, H., Razeghi, P., Shiojima, I., Sandri, M., Sato, K., Zeng, L., Schiekofer, S., Pimentel, D., Lecker, S., Taegtmeyer, H., Goldberg, A. L., & Walsh, K.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 280
- Issue
- 21
- Pages
- 20814-20823
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2139089901
- Cited by
- 353
- References
- 57
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Skurk, C., Izumiya, Y., Maatz, H., Razeghi, P., Shiojima, I., Sandri, M., Sato, K., Zeng, L., Schiekofer, S., Pimentel, D., Lecker, S., Taegtmeyer, H., Goldberg, A. L., & Walsh, K. (2005). The FOXO3a Transcription Factor Regulates Cardiac Myocyte Size Downstream of AKT Signaling. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m500528200
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