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SIRT1 Promotes Proliferation and Prevents Senescence Through Targeting LKB1 in Primary Porcine Aortic Endothelial Cells
Open accessAbstract
RATIONALE: Endothelial senescence causes endothelial dysfunction, promotes atherogenesis and contributes to age-related vascular disorders. SIRT1 is a conserved NAD(+)-dependent deacetylase possessing beneficial effects against aging-related diseases, despite that the detailed functional mechanisms are largely uncharacterized. OBJECTIVE: The present study is designed to evaluate the protective effects of SIRT1 on endothelial senescence and to elucidate the underlying mechanisms. METHODS AND RESULTS: An in vitro senescence model was established by prolonged culture of primary endothelial cells isolated from porcine aorta. The freshly isolated "young" cells gradually underwent senescence during 1 month of repetitive passages. Both mRNA and protein expressions of SIRT1 were progressively decreased. In contrast, the protein levels of LKB1, a serine/threonine kinase and tumor suppressor, and the phosphorylation of its downstream target AMPK(Thr172) were dramatically increased in senescent cells. Overexpression of LKB1 promoted cellular senescence and retarded endothelial proliferation, which could be blocked by increasing SIRT1 levels. Knocking down of SIRT1 induced senescence and elevated the protein levels of LKB1 and phosphorylated AMPK(Thr172). Regardless of the nutritional status, hyperactivation of AMPK was able to induce endothelial senescence. SIRT1 antagonized LKB1-dependent AMPK activation through promoting the deacetylation, ubiquitination and proteasome-mediated degradation of LKB1. The survival signaling of Akt was also found to be modulated by SIRT1 and LKB1, and could cross-regulate AMPK activity. CONCLUSIONS: SIRT1 and LKB1/AMPK are the 2 key sensor systems for regulating endothelial cell survival, proliferation and senescence. The protective activities of SIRT1 may be achieved at least in part by fine tuning the acetylation/deacetylation status and stabilities of LKB1 protein.
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“Sirtuin-1 also has been reported to promote endothelial cell proliferation and suppress senescence of porcine primary aortic endothelial cells via a signaling mechanism requiring the expression of the serine-threonine kinase, LKB1, the upstream regulator of AMPK (179).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [179]
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3 retracted
Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo
Zou, M., Kirkpatrick, S. S., Davis, B. J., Nelson, J. S., Wiles, W. G., Schlattner, U., Neumann, D., Brownlee, M., Freeman, M. B., & Goldman, M. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404421200 · Cited by 480
RetractedChoi, H. C., Song, P., Xie, Z., Wu, Y., Xu, J., Zhang, M., Dong, Y., Wang, S., Lau, K., & Zou, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803020200 · Cited by 85
RetractedSong, P., Xie, Z., Wu, Y., Xu, J., Dong, Y., & Zou, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708208200 · Cited by 74
RetractedAMPK 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
AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
Hardie, D. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2249 · Cited by 2,261
Sirtuins in mammals: insights into their biological function
Michán, S., & Sinclair, D. A. (2007) · Biochemical Journal · doi:10.1042/bj20070140 · Cited by 1,750
LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G. D., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., & Carling, D. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.031 · Cited by 1,650
AMP-activated protein kinase induces a p53-dependent metabolic checkpoint
Jones, R. G., Plas, D. R., Kubek, S., Buzzai, M., Mu, J., Xu, Y., Birnbaum, M. J., & Thompson, C. B. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.03.027 · Cited by 1,619
A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy
Lee, I. H., Cao, L., Mostoslavsky, R., Lombard, D. B., Liu, J., Bruns, N. E., Tsokos, M., Alt, F. W., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712145105 · Cited by 1,510
Mattagajasingh, I., Kim, C.-S., Naqvi, A., Yamamori, T., Hoffman, T. A., Jung, S.-B., DeRicco, J., Kasuno, K., & Irani, K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704329104 · Cited by 881
Fulco, M., Cen, Y., Zhao, P., Hoffman, E. P., McBurney, M. W., Sauve, A. A., & Sartorelli, V. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.02.004 · Cited by 843
SIRT1 Modulation of the Acetylation Status, Cytosolic Localization, and Activity of LKB1
Lan, F., Cacicedo, J. M., Ruderman, N., & Ido, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805711200 · Cited by 825
LKB1-Dependent Signaling Pathways
Alessi, D. R., Sakamoto, K., & Bayascas, J. R. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142702 · Cited by 805
SIRT1 Regulates Hepatocyte Lipid Metabolism through Activating AMP-activated Protein Kinase
Hou, X., Xu, S., Maitland-Toolan, K. A., Sato, K., Jiang, B., Ido, Y., Lan, F., Walsh, K., Wierzbicki, M., Verbeuren, T. J., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802187200 · Cited by 778
A complex interplay between Akt, TSC2 and the two mTOR complexes
Huang, J., & Manning, B. D. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370217 · Cited by 724
Resveratrol stimulates AMP kinase activity in neurons
Dasgupta, B., & Milbrandt, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610068104 · Cited by 723
SIRT1 Controls Endothelial Angiogenic Functions During Vascular Growth
Potente, M., Ghaeni, L., Baldessari, D., Mostoslavsky, R., Rossig, L., Dequiedt, F., Haendeler, J., Mione, M., Dejana, E., Alt, F. W., et al. (2007) · Genes & Development · doi:10.1101/gad.435107 · Cited by 608
BRANDES, R., FLEMING, I., & BUSSE, R. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.12.027 · Cited by 563
AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome
Ruderman, N., & Prentki, M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1344 · Cited by 451
Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation
Bardeesy, N. M., Sinha, M., Hezel, A. F., Signoretti, S., Hathaway, N. A., Sharpless, N. E., Loda, M. F., Carrasco, D. R., & DePinho, R. A. (2002) · Nature · doi:10.1038/nature01045 · Cited by 435
Horman, S., Vertommen, D., Heath, R. B., Neumann, D., Mouton, V., Woods, A., Schlattner, U., Wallimann, T., Carling, D., Hue, L., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506850200 · Cited by 355
Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival
Narbonne, P., & Roy, R. (2008) · Nature · doi:10.1038/nature07536 · Cited by 324
Vascular Abnormalities and Deregulation of VEGF in Lkb1 -Deficient Mice
Ylikorkala, A., Rossi, D. J., Korsisaari, N., Luukko, K., Alitalo, K. K., Henkemeyer, M. J., & Mäkelä, T. P. (2001) · Science · doi:10.1126/science.1062074 · Cited by 299
Xie, Z., Dong, Y., Scholz, R., Neumann, D., & Zou, M.-H. (2008) · Circulation · doi:10.1161/circulationaha.107.744490 · Cited by 273
Protein Kinase B/Akt Prevents Fatty Acid-induced Apoptosis in Pancreatic β-Cells (INS-1)
Wrede, C. E., Dickson, L. M., Lingohr, M. K., Briaud, I., & Rhodes, C. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208756200 · Cited by 246
Wang, W., Yang, X., López de Silanes, I., Carling, D., & Gorospe, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300318200 · Cited by 243
Ota, H., Eto, M., Kano, M. R., Ogawa, S., Iijima, K., Akishita, M., & Ouchi, Y. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.164368 · Cited by 227
Zhang, Y., Lee, T.-S., Kolb, E. M., Sun, K., Lu, X., Sladek, F. M., Kassab, G. S., Garland, T., & Shyy, J. Y.-J. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000221230.08596.98 · Cited by 212
Shin, S. M., Cho, I. J., & Kim, S. G. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.058479 · Cited by 197
Kume, S., Haneda, M., Kanasaki, K., Sugimoto, T., Araki, S.-I., Isono, M., Isshiki, K., Uzu, T., Kashiwagi, A., & Koya, D. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.02.014 · Cited by 176
A therapeutic role for sirtuins in diseases of aging?
Westphal, C. H., Dipp, M., & Guarente, L. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.09.008 · Cited by 168
Gottdiener, J. S., Maron, B. J., Schooley, R., Harley, J. B., Roberts, W. C., & Fauci, A. S. (1983) · Circulation · doi:10.1161/01.cir.67.3.572 · Cited by 164
Emerging roles of SIRT1 in vascular endothelial homeostasis
Potente, M., & Dimmeler, S. (2008) · Cell Cycle · doi:10.4161/cc.7.14.6267 · Cited by 158
Endothelial Control of Vasomotor Function-From Health to Coronary Disease-
Vanhoutte, P. M. (2003) · Circulation Journal · doi:10.1253/circj.67.572 · Cited by 151
Self-citationPremature aging in mice activates a systemic metabolic response involving autophagy induction
Mariño, G., Ugalde, A. P., Salvador-Montoliu, N., Varela, I., Quirós, P. M., Cadiñanos, J., van der Pluijm, I., Freije, J. M. P., & López-Otı́n, C. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn120 · Cited by 144
Thomson, D. M., & Gordon, S. E. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00811.2004 · Cited by 131
High glucose downregulates endothelial progenitor cell number via SIRT1
Balestrieri, M. L., Rienzo, M., Felice, F., Rossiello, R., Grimaldi, V., Milone, L., Casamassimi, A., Servillo, L., Farzati, B., Giovane, A., et al. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2008.03.004 · Cited by 117
Law, I. K. M., Liu, L., Xu, A., Lam, K. S. L., Vanhoutte, P. M., Che, C., Leung, P. T. Y., & Wang, Y. (2009) · PROTEOMICS · doi:10.1002/pmic.200800738 · Cited by 114
Self-citationNarala, S. R., Allsopp, R. C., Wells, T. B., Zhang, G., Prasad, P., Coussens, M. J., Rossi, D. J., Weissman, I. L., & Vaziri, H. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-09-0965 · Cited by 106
Xie, Z., Dong, Y., Zhang, J., Scholz, R., Neumann, D., & Zou, M. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01417-08 · Cited by 102
Mechanisms of endothelial senescence
Erusalimsky, J. D., & Skene, C. (2008) · Experimental Physiology · doi:10.1113/expphysiol.2008.043133 · Cited by 97
Lam, J. B. B., Chow, H., Xu, A., Lam, K. S. L., Liu, J., Wong, N.-S., Moon, R. T., Shepherd, P. R., Cooper, G. J. S., & Wang, Y. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004968 · Cited by 85
Self-citationSirolimus and Everolimus Induce Endothelial Cellular Senescence Via Sirtuin 1 Down-Regulation
Ota, H., Eto, M., Ako, J., Ogawa, S., Iijima, K., Akishita, M., & Ouchi, Y. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.01.072 · Cited by 79
Genomic Changes in Regenerated Porcine Coronary Arterial Endothelial Cells
Lee, M. Y. K., Tse, H., Siu, C., Zhu, S., Man, R. Y. K., & Vanhoutte, P. M. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.141705 · Cited by 61
Self-citationMulligan, J. D., Gonzalez, A. A., Kumar, R., Davis, A. J., & Saupe, K. W. (2005) · The Journals of Gerontology Series A · doi:10.1093/gerona/60.1.21 · Cited by 50
Down-regulation of AMP-activated protein kinase by calorie restriction in rat liver
To, K., Yamaza, H., Komatsu, T., Hayashida, T., Hayashi, H., Toyama, H., Chiba, T., Higami, Y., & Shimokawa, I. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.07.003 · Cited by 44
Londesborough, A., Vaahtomeri, K., Tiainen, M., Katajisto, P., Ekman, N., Vallenius, T., & Mäkelä, T. P. (2008) · Development · doi:10.1242/dev.017038 · Cited by 44
Senescence and its bypass in the vascular endothelium
Deborah, A. F. (2005) · Frontiers in bioscience · doi:10.2741/1588 · Cited by 13
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Metadata
- Authors
- Zu, Y., Liu, L., Lee, M. Y. K., Xu, C., Liang, Y., Man, R. Y., Vanhoutte, P. M., & Wang, Y.
- Affiliations
- University of Hong Kong (HK)
- Venue
- Circulation Research
- Published
- 2010-04-30
- Volume
- 106
- Issue
- 8
- Pages
- 1384-1393
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W1964041100
- Cited by
- 303
- References
- 48
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 11 · 2023: 13 · 2022: 25 · 2021: 19 · 2020: 21 · 2019: 15 · 2018: 23 · 2017: 16 · 2016: 19 · 2015: 24 · 2014: 25 · 2013: 20 · 2012: 28
- FWCI
- 8.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- SIRT1, LKB1, AMPK, endothelial cell senescence, endothelial cell proliferation, endothelial cell survival, protein deacetylation, ubiquitination, proteasomal degradation, Akt signaling, aortic endothelial cells, atherogenesis
- MeSH terms
- Acetylation, Animals, Aorta, Cell Survival, Cells, Cultured, Enzyme Activation, Female, Genotype, Humans, Injections, Intraperitoneal, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Paraquat, Phenotype, Phosphorylation, Protein Processing, Post-Translational, RNA, Messenger, Swine, Threonine, Time Factors, Transfection, Signal Transduction, Down-Regulation, Up-Regulation, Cellular Senescence, Protein Serine-Threonine Kinases, RNA Interference, Endothelial Cells, Proteasome Endopeptidase Complex, Cell Proliferation, Proto-Oncogene Proteins c-akt, Mice, Ubiquitination, AMP-Activated Protein Kinases, Sirtuin 1
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