The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
Exogenous NAD Blocks Cardiac Hypertrophic Response via Activation of the SIRT3-LKB1-AMP-activated Kinase Pathway
Open accessAbstract
Since the discovery of NAD-dependent deacetylases, sirtuins, it has been recognized that maintaining intracellular levels of NAD is crucial for the management of stress response of cells. Here we show that agonist-induced cardiac hypertrophy is associated with loss of intracellular levels of NAD, but not exercise-induced physiologic hypertrophy. Exogenous addition of NAD was capable of maintaining intracellular levels of NAD and blocking the agonist-induced cardiac hypertrophic response in vitro as well as in vivo. NAD treatment blocked the activation of pro-hypertrophic Akt1 signaling, and augmented the activity of anti-hypertrophic LKB1-AMPK signaling in the heart, which prevented subsequent induction of mTOR-mediated protein synthesis. By using gene knock-out and transgenic mouse models of SIRT3 and SIRT1, we showed that the anti-hypertrophic effects of exogenous NAD are mediated through activation of SIRT3, but not SIRT1. SIRT3 deacetylates and activates LKB1, thus augmenting the activity of the LKB1-AMPK pathway. These results reveal a novel role of NAD as an inhibitor of cardiac hypertrophic signaling, and suggest that prevention of NAD depletion may be critical in the treatment of cardiac hypertrophy and heart failure.
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Cites
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300
Regulation of cardiac hypertrophy by intracellular signalling pathways
Heineke, J., & Molkentin, J. D. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1983 · Cited by 1,866
Hawley, S. A., Boudeau, J., Reid, J. L., Mustard, K. J., Udd, L., Mäkelä, T. P., Alessi, D. R., & Hardie, D. G. (2003) · Journal of Biology · doi:10.1186/1475-4924-2-28 · Cited by 1,665
Cardiac Hypertrophy: The Good, the Bad, and the Ugly
Frey, N., & Olson, E. N. (2003) · Annual Review of Physiology · doi:10.1146/annurev.physiol.65.092101.142243 · Cited by 1,449
Michishita, E., Park, J. Y., Burneskis, J. M., Barrett, J. C., & Horikawa, I. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-01-0033 · Cited by 1,364
Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
Haigis, M. C., & Guarente, L. P. (2006) · Genes & Development · doi:10.1101/gad.1467506 · Cited by 1,295
A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis
Ahn, B.-H., Kim, H.-S., Song, S., Lee, I. H., Liu, J., Vassilopoulos, A., Deng, C.-X., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803790105 · Cited by 1,291
Sirt1 Regulates Aging and Resistance to Oxidative Stress in the Heart
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Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice
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Cited by
Cardiac Energy Metabolism in Heart Failure
Lopaschuk, G. D., Karwi, Q. G., Tian, R., Wende, A. R., & Abel, E. D. (2021) · Circulation Research · doi:10.1161/circresaha.121.318241 · Cited by 1,373
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
Physiological and pathological cardiac hypertrophy
Shimizu, I., & Minamino, T. (2016) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2016.06.001 · Cited by 887
Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling
Verdin, E., Hirschey, M. D., Finley, L. W. S., & Haigis, M. C. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.003 · Cited by 661
“Indeed, recent studies have shown that SIRT3 regulates AMPK activation [56-58].”
BackgroundNAD+ homeostasis in health and disease
Katsyuba, E., Romani, M., Hofer, D., & Auwerx, J. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0161-5 · Cited by 627
Metadata
- Authors
- Pillai, V. B., Sundaresan, N. R., Kim, G., Gupta, M., Rajamohan, S. B., Pillai, J. B., Samant, S., Ravindra, P. V., Isbatan, A., & Gupta, M. P.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 285
- Issue
- 5
- Pages
- 3133-3144
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2082740501
- Cited by
- 419
- References
- 50
- FWCI
- 13.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Exogenous NAD Blocks Cardiac Hypertrophic Response via Activation of the SIRT3-LKB1-AMP-activated Kinase Pathway. https://app.cochat.ai/papers/10.1074/jbc.m109.077271
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- Pillai, V. B., Sundaresan, N. R., Kim, G., Gupta, M., Rajamohan, S. B., Pillai, J. B., Samant, S., Ravindra, P. V., Isbatan, A., & Gupta, M. P. (2010). Exogenous NAD Blocks Cardiac Hypertrophic Response via Activation of the SIRT3-LKB1-AMP-activated Kinase Pathway. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m109.077271
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
