Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia
Abstract
Diabetic hyperglycaemia causes endothelial dysfunction mainly by impairing endothelial nitric oxide (NO) production. Moreover, hyperglycaemia activates several noxious cellular pathways including apoptosis, increase in reactive oxygen species (ROS) levels and diminishing Na(+)-K(+) ATPase activity which exacerbate vascular damage. Serum glucocorticoid kinase (SGK)-1, a member of the serine/threonine kinases, plays a pivotal role in regulating NO production through inducible NO synthase activation and other cellular mechanisms. Therefore, in this study, we aimed to investigate the protective role of SGK-1 against hyperglycaemia in human umbilical endothelial cells (HUVECs). We used retrovirus to infect HUVECs with either SGK-1, SGK-1Δ60 (lacking of the N-60 amino acids-increase SGK-1 activity) or SGK-1Δ60KD (kinase-dead constructs). We tested our hypothesis in vitro after high glucose and glucosamine incubation. Increase in SGK-1 expression and activity (SGK-1Δ60) resulted in higher production of NO, inhibition of ROS synthesis and lower apoptosis in endothelial cell after either hyperglycaemia or glucosamine treatments. Moreover, in this study, we showed increased GLUT-1 membrane translocation and Na(+)-K(+) ATPase activity in cell infected with SGK-1Δ60 construct. These results suggest that as in endothelial cells, an increased SGK-1 activity and expression reduces oxidative stress, improves cell survival and restores insulin-mediated NO production after different noxae stim…
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SGK1 is a potent antioxidant and has been implicated in pathogenesis of Huntington's disease.
“SGK1 is a potent antioxidant and has been implicated in the pathogenesis of HD”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Ferrelli et al., 2015
Cites
The Pathobiology of Diabetic Complications
Brownlee, M. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1615 · Cited by 5,339 · see citing works
Oxidative Stress and Cardiovascular Injury
Griendling, K. K., & FitzGerald, G. A. (2003) · Circulation · doi:10.1161/01.cir.0000093660.86242.bb · Cited by 940 · see citing works
García-Martínez, J. M., & Alessi, D. R. (2008) · Biochemical Journal · doi:10.1042/bj20081668 · Cited by 907 · see citing works
Brunet, A., Park, J., Tran, H., Hu, L. S., Hemmings, B. A., & Greenberg, M. E. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.3.952-965.2001 · Cited by 860 · see citing works
Endothelial Function Testing as a Biomarker of Vascular Disease
Verma, S., Buchanan, M. R., & Anderson, T. J. (2003) · Circulation · doi:10.1161/01.cir.0000089191.72957.ed · Cited by 565 · see citing works
Post, R. L., Sen, A. K., & Rosenthal, A. S. (1965) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)97594-0 · Cited by 480 · see citing works
Waldegger, S., Barth, P., Raber, G., & Lang, F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4440 · Cited by 367 · see citing works
Endothelial dysfunction and diabetes: roles of hyperglycemia, impaired insulin signaling and obesity
Bakker, W., Eringa, E. C., Sipkema, P., & van Hinsbergh, V. W. M. (2008) · Cell and Tissue Research · doi:10.1007/s00441-008-0685-6 · Cited by 343 · see citing works
Oxidative stress in vascular disease and its pharmacological prevention
Li, H., Horke, S., & Förstermann, U. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.03.007 · Cited by 321 · see citing works
Mikosz, C. A., Brickley, D. R., Sharkey, M. S., Moran, T. W., & Conzen, S. D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010842200 · Cited by 271 · see citing works
Serum and glucocorticoid‐regulated protein kinases: Variations on a theme
Tessier, M., & Woodgett, J. R. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20894 · Cited by 175 · see citing works
The physiological impact of the serum and glucocorticoid-inducible kinase SGK1
Lang, F., Artunc, F., & Vallon, V. (2009) · Current Opinion in Nephrology and Hypertension · doi:10.1097/mnh.0b013e32832f125e · Cited by 139 · see citing works
Dehner, M., Hadjihannas, M. V., Weiske, J., Huber, O., & Behrens, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710366200 · Cited by 116 · see citing works
Handa, O., Stephen, J., & Cepinskas, G. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00476.2008 · Cited by 100 · see citing works
Sgk1, a cell survival response in neurodegenerative diseases.
Schoenebeck, B., Bader, V., Zhu, X.-R., Schmitz, B., Lübbert, H., & Stichel, C. (2005) · Molecular and cellular neurosciences · doi:10.1016/j.mcn.2005.07.017 · Cited by 85 · see citing works
Failor, K. L., Desyatnikov, Y., Finger, L. A., & Firestone, G. L. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0143 · Cited by 76 · see citing works
Thiazolidinedione-Induced Fluid Retention: Recent Insights into the Molecular Mechanisms
Bełtowski, J., Rachańczyk, J., & Włodarczyk, M. (2013) · PPAR Research · doi:10.1155/2013/628628 · Cited by 74 · see citing works
Role of cellular mechanics in the function and life span of vascular endothelium
Kliche, K., Jeggle, P., Pavenstädt, H., & Oberleithner, H. (2011) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-011-0929-2 · Cited by 73 · see citing works
SGK1 Kinase Upregulates GLUT1 Activity and Plasma Membrane Expression
Palmada, M., Boehmer, C., Akel, A., Rajamanickam, J., Jeyaraj, S., Keller, K., & Lang, F. (2006) · Diabetes · doi:10.2337/diabetes.55.02.06.db05-0720 · Cited by 71 · see citing works
Kemeny, S. F., Figueroa, D. S., & Clyne, A. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066176 · Cited by 68 · see citing works
Role of SGK1 in nitric oxide inhibition of ENaC in Na+-transporting epithelia
Helms, M. N., Yu, L., Malik, B., Kleinhenz, D. J., Hart, C. M., & Eaton, D. C. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00006.2005 · Cited by 63 · see citing works
Association of SGK1 Gene Polymorphisms with Type 2 Diabetes
Schwab, M. G., Lupescu, A., Moța, M., Moța, E., Frey, A., Simon, P. D., Mertens, P. R., Floege, J., Luft, F. C., Asante-Poku, S., et al. (2008) · Cellular Physiology and Biochemistry · doi:10.1159/000113757 · Cited by 61 · see citing works
Duan, W., Paka, L., & Pillarisetti, S. (2005) · Cardiovascular Diabetology · doi:10.1186/1475-2840-4-16 · Cited by 58 · see citing works
Rao, A. D., Sun, B., Saxena, A. R., Hopkins, P. N., Jeunemaı̂tre, X., Brown, N. J., Adler, G. K., & Williams, J. S. (2012) · Journal of Human Hypertension · doi:10.1038/jhh.2012.22 · Cited by 53 · see citing works
de la Rosa, D. Á., Coric, T., Todorović, N. V., Shao, D., Wang, T., & Canessa, C. M. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.042903 · Cited by 53 · see citing works
Analysis of differentially expressed genes in nitric oxide-exposed human monocytic cells
Turpaev, K. T., Bouton, C., Diet, A., Glatigny, A., & Drapier, J. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.02.002 · Cited by 47 · see citing works
Serum- and Glucocorticoid-Inducible Kinase 1 Mediates Salt Sensitivity of Glucose Tolerance
Boini, K. M., Hennige, A. M., Huang, D. Y., Friedrich, B., Palmada, M., Boehmer, C., Grahammer, F., Artunç, F., Ullrich, S., Avram, D., et al. (2006) · Diabetes · doi:10.2337/db05-1038 · Cited by 43 · see citing works
Engelsberg, A., Kobelt, F., & Kuhl, D. (2006) · Biochemical Journal · doi:10.1042/bj20060386 · Cited by 30 · see citing works
Yamasaki, Y., Kim, Y.-S., & Kawamori, R. (2006) · Cardiovascular Diabetology · doi:10.1186/1475-2840-5-16 · Cited by 15 · see citing works
Enhanced Expression of Serum and Glucocorticoid-Inducible Kinase-1 in Kidneys of L-NAME-Treated Rats
Feng, Y., Wang, Y., Xiong, J., Liu, Z., Yard, B. A., & Lang, F. J. W. (2006) · Kidney & Blood Pressure Research · doi:10.1159/000093461 · Cited by 10 · see citing works
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Talarico, C., Dattilo, V., D’Antona, L., Barone, A., Amodio, N., Belviso, S., Musumeci, F., Abbruzzese, C., Bianco, C., Trapasso, F., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.7520 · Cited by 72 · see citing works
Ueda, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23074010 · Cited by 70 · see citing works
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Lou, Y., Hu, M., Mao, L., Zheng, Y., & Jin, F. (2016) · The FASEB Journal · doi:10.1096/fj.201600760r · Cited by 37 · see citing works
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Pastore, D., Della-Morte, D., Coppola, A., Capuani, B., Lombardo, M., Pacifici, F., Ferrelli, F., Arriga, R., Mammi, C., Federici, M., et al. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.232 · Cited by 33 · see citing works
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Wang, M., Xue, Y., Shen, L., Qin, P., Sang, X., Tao, Z., Yi, J., Wang, J., Liu, P.-X., & Cheng, H.-L. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101225 · Cited by 33 · see citing works
Jiang, D., Fu, C., Xiao, J., Zhang, Z., Zou, J., Ye, Z., & Zhang, X. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2013594 · Cited by 31 · see citing works
Basello, K., Pacifici, F., Capuani, B., Pastore, D., Lombardo, M. F., Ferrelli, F., Coppola, A., Donadel, G., Arriga, R., Sconocchia, G., et al. (2015) · Rejuvenation Research · doi:10.1089/rej.2015.1726 · Cited by 19 · see citing works
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Rea, S., Della‐Morte, D., Pacifici, F., Capuani, B., Pastore, D., Coppola, A., Arriga, R., Andreadi, A., Donadel, G., Daniele, N. D., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00779 · Cited by 17 · see citing works
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Ruiz-Laguna, J., Vélez, J. M., Pueyo, C., & Abril, N. (2015) · Environmental Science and Pollution Research · doi:10.1007/s11356-015-5824-5 · Cited by 14 · see citing works
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Howard, P. G., Zou, P., Zhang, Y., Huang, F., Tesic, V., Wu, C. Y.-C., & Lee, R. H.-C. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114973 · Cited by 13 · see citing works
Sun, Z., Lawson, D. A., Sinclair, E., Wang, C., Lai, M.-D., Hetts, S. W., Higashida, R. T., Dowd, C. F., Halbach, V. V., Werb, Z., et al. (2015) · Biotechnology Reports · doi:10.1016/j.btre.2015.07.001 · Cited by 12 · see citing works
Zhao, N., Geng, P., Perez, A. G., Maya, A. C., Yadav, B. S., Du, Y., & Ge, Y. (2025) · mSystems · doi:10.1128/msystems.00790-25 · Cited by 11 · see citing works
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Akhoon, B. A., Gandhi, N. S., & Pandey, R. (2019) · Biochimie · doi:10.1016/j.biochi.2019.07.007 · Cited by 9 · see citing works
Martín-Batista, E., Maglio, L. E., Armas-Capote, N., Hernández, G., de la Rosa, D. Á., & Giráldez, T. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105317 · Cited by 8 · see citing works
Meduri, G. U., & Chrousos, G. P. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-817558-3.00012-3 · Cited by 7 · see citing works
E-Fatima, J., Khan, F. I., & Lai, D. (2025) · Heart Rhythm O2 · doi:10.1016/j.hroo.2025.02.015 · Cited by 5 · see citing works
Mushab, M., Hairrudin, H., & Abrori, C. (2020) · Jurnal Kesehatan Andalas · doi:10.25077/jka.v9i2.1312 · Cited by 4 · see citing works
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Unraveling the Potential of SGK1 in Osteoporosis: From Molecular Mechanisms to Therapeutic Targets
Yang, F., Chen, C., Chen, R., Yang, C., Liu, Z., Wen, L., Xiao, H., Geng, B., & Xia, Y. (2025) · Biomolecules · doi:10.3390/biom15050686 · Cited by 3 · see citing works
Arnal, E., Johnsen‐Soriano, S., López-Malo, D., Pérez-Pastor, G. M. A., Vidal‐Gil, L., Morillas-Carrasco, N., Sancho-Pellúz, J., Romero, F. J., & Barcia, J. M. (2016) · doi:10.20455/ros.2016.843 · Cited by 2 · see citing works
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Self-citation
- Authors
- Ferrelli, F., Pastore, D., Capuani, B., Lombardo, M. F., Blot-Chabaud, M., Coppola, A., Basello, K., Galli, A., Donadel, G., Romano, M., Caratelli, S., Pacifici, F., Arriga, R., Di Daniele, N., Sbraccia, P., Sconocchia, G., Bellia, A., Tesauro, M., Federici, M., Della-Morte, D., & Lauro, D.
- Affiliations
- University of Rome Tor Vergata (IT)
- Policlinico Tor Vergata (IT)
- Istituto di Farmacologia Traslazionale (IT)
- Corresponding author
- Lauro, Davide
- ORCID
- Venue
- Acta Diabetologica
- Published
- 2014-06-25
- Volume
- 52
- Issue
- 1
- Pages
- 55-64
- ISSN
- 0940-5429 (ISSN-L)
- 1432-5233
- OpenAlex
- W2083114966
- Cited by
- 30
- References
- 30
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 3 · 2017: 1 · 2016: 5 · 2015: 4
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Diabetologica (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- SGK1, endothelial dysfunction, hyperglycemia, oxidative stress, apoptosis, endothelial nitric oxide production, reactive oxygen species, Na+/K+-ATPase, glucosamine, diabetic vascular disease, human umbilical vein endothelial cells
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Cell Line, Glucose, Humans, Hyperglycemia, Insulin, Nitric Oxide, Apoptosis, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Oxidative Stress, Human Umbilical Vein Endothelial Cells
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