The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Downregulation of MiR-199a Derepresses Hypoxia-Inducible Factor-1α and Sirtuin 1 and Recapitulates Hypoxia Preconditioning in Cardiac Myocytes
Open accessAbstract
MicroRNAs are posttranscriptional gene regulators that are differentially expressed during various diseases and have been implicated in the underlying pathogenesis. We report here that miR-199a is acutely downregulated in cardiac myocytes on a decline in oxygen tension. This reduction is required for the rapid upregulation of its target, hypoxia-inducible factor (Hif)-1α. Replenishing miR-199a during hypoxia inhibits Hif-1α expression and its stabilization of p53 and, thus, reduces apoptosis. On the other hand, knockdown of miR-199a during normoxia results in the upregulation of Hif-1α and Sirtuin (Sirt)1 and reproduces hypoxia preconditioning. Sirt1 is also a direct target of miR-199a and is responsible for downregulating prolyl hydroxylase 2, required for stabilization of Hif-1α. Thus, we conclude that miR-199a is a master regulator of a hypoxia-triggered pathway and can be exploited for preconditioning cells against hypoxic damage. In addition, the data demonstrate a functional link between 2 key molecules that regulate hypoxia preconditioning and longevity.
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1 retracted
Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
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Cited by
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085
Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008
Pervasive roles of microRNAs in cardiovascular biology
Small, E. M., & Olson, E. N. (2011) · Nature · doi:10.1038/nature09783 · Cited by 1,180
MicroRNAs in Development and Disease
Sayed, D., & Abdellatif, M. (2011) · Physiological Reviews · doi:10.1152/physrev.00006.2010 · Cited by 1,078
Self-citationFunctional screening identifies miRNAs inducing cardiac regeneration
Eulalio, A., Mano, M., Ferro, M. D., Zentilin, L., Sinagra, G., Zacchigna, S., & Giacca, M. (2012) · Nature · doi:10.1038/nature11739 · Cited by 1,029
Metadata
- Authors
- Rane, S., He, M., Sayed, D., Vashistha, H., Malhotra, A., Sadoshima, J., Vatner, D. E., Vatner, S. F., & Abdellatif, M.
- Venue
- Circulation Research
- Published
- 2009-04-10
- Volume
- 104
- Issue
- 7
- Pages
- 879-886
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2170945707
- Cited by
- 578
- References
- 35
- FWCI
- 16.03
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Downregulation of MiR-199a Derepresses Hypoxia-Inducible Factor-1α and Sirtuin 1 and Recapitulates Hypoxia Preconditioning in Cardiac Myocytes. https://app.cochat.ai/papers/10.1161/circresaha.108.193102
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- Rane, S., He, M., Sayed, D., Vashistha, H., Malhotra, A., Sadoshima, J., Vatner, D. E., Vatner, S. F., & Abdellatif, M. (2009). Downregulation of MiR-199a Derepresses Hypoxia-Inducible Factor-1α and Sirtuin 1 and Recapitulates Hypoxia Preconditioning in Cardiac Myocytes. Circulation Research. https://doi.org/10.1161/circresaha.108.193102
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