The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice
Open accessAbstract
Sirtuin 3 (SIRT3) is a member of the sirtuin family of proteins that promote longevity in many organisms. Increased expression of SIRT3 has been linked to an extended life span in humans. Here, we have shown that Sirt3 protects the mouse heart by blocking the cardiac hypertrophic response. Although Sirt3-deficient mice appeared to have normal activity, they showed signs of cardiac hypertrophy and interstitial fibrosis at 8 weeks of age. Application of hypertrophic stimuli to these mice produced a severe cardiac hypertrophic response, whereas Sirt3-expressing Tg mice were protected from similar stimuli. In primary cultures of cardiomyocytes, Sirt3 blocked cardiac hypertrophy by activating the forkhead box O3a-dependent (Foxo3a-dependent), antioxidant-encoding genes manganese superoxide dismutase (MnSOD) and catalase (Cat), thereby decreasing cellular levels of ROS. Reduced ROS levels suppressed Ras activation and downstream signaling through the MAPK/ERK and PI3K/Akt pathways. This resulted in repressed activity of transcription factors, specifically GATA4 and NFAT, and translation factors, specifically eukaryotic initiation factor 4E (elf4E) and S6 ribosomal protein (S6P), which are involved in the development of cardiac hypertrophy. These results demonstrate that SIRT3 is an endogenous negative regulator of cardiac hypertrophy, which protects hearts by suppressing cellular levels of ROS.
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Cites
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Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation
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Cited by
Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release
Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2014) · Physiological Reviews · doi:10.1152/physrev.00026.2013 · Cited by 5,383
The intersection between aging and cardiovascular disease
North, B. J., & Sinclair, D. A. (2012) · Circulation Research · doi:10.1161/circresaha.111.246876 · Cited by 1,585
Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation
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NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential
Xie, N., Zhang, L., Gao, W., Huang, C., Huber, P. E., Zhou, X., Li, C., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,052
Metadata
- Authors
- Sundaresan, N. R., Gupta, M., Kim, G., Rajamohan, S. B., Isbatan, A., & Gupta, M. P.
- Venue
- Journal of Clinical Investigation
- Published
- 2009-08-03
- Volume
- 119
- Issue
- 9
- Pages
- 2758-71
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2049266192
- Cited by
- 995
- References
- 9
- FWCI
- 29.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Sundaresan, N. R., Gupta, M., Kim, G., Rajamohan, S. B., Isbatan, A., & Gupta, M. P. (2009). Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. Journal of Clinical Investigation. https://doi.org/10.1172/jci39162
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