title: Serum- and Glucocorticoid-Inducible Kinase 1 Delay the Onset of Endothelial Senescence by Directly Interacting with Human Telomerase Reverse Transcriptase.
abstract: Endothelial senescence is characteristic of vascular aging. Serum- and glucocorticoid-inducible kinase (SGK)1 belongs to a family of serine/threonine kinases regulated by various external stimuli. SGK1 has been shown to be protective against reactive oxygen species (ROS) production and to be involved in processes regulating aging. However, data on the direct relationship between SGK1 and senescence are sparse. In the present study, we sought to investigate the role of SGK1 in cellular aging by using human umbilical vein endothelial cells (HUVECs) infected with different constructs. Senescence was measured at different cellular stages by senescence-associated β-galactosidase (SA-β-gal) activity, human telomerase reverse transcriptase (hTERT) activity, p21 protein levels, and ROS production. HUVECs over-expressing full-length SGK1 (wild-type SGK1 [SGK1WT]) showed a decrease in SA-β-gal and p21 expression and a corresponding increase in hTERT activity in the early stages of aging. Moreover, SGK1WT presented lower levels of ROS production. A direct interaction between SGK1WT and hTERT was also shown by co-immunoprecipitation. The SGK1Δ60 isoform, lacking the amino-terminal 60 amino acids, did not show interaction with hTERT, suggesting a pivotal role of this protein site for the SGK1 anti-aging function. The results from this study may be of particular importance, because SGK1WT over-expression by activating telomerase and reducing ROS levels may delay the processes of endothelial senescence.
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Katia
authors.initials: K
authors.lastname: Basello
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Francesca
authors.initials: F
authors.lastname: Pacifici
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Barbara
authors.initials: B
authors.lastname: Capuani
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Donatella
authors.initials: D
authors.lastname: Pastore
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Marco F
authors.initials: MF
authors.lastname: Lombardo
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrelli
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Andrea
authors.initials: A
authors.lastname: Coppola
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Giulia
authors.initials: G
authors.lastname: Donadel
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Roberto
authors.initials: R
authors.lastname: Arriga
authors.affiliation: 2 Institute of Translational Pharmacology , National Research Council, Rome, Italy .
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sconocchia
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Alfonso
authors.initials: A
authors.lastname: Bellia
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Paola
authors.initials: P
authors.lastname: Rogliani
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Massimo
authors.initials: M
authors.lastname: Federici
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Paolo
authors.initials: P
authors.lastname: Sbraccia
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.affiliation: 1 Department of Systems Medicine, University of Rome Tor Vergata , Italy .|3 IRCCS San Raffaele Pisana , Rome, Italy .
authors.forename: David
authors.initials: D
authors.lastname: Della-Morte
mesh_terms: D016922:Cellular Senescence; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000201:enzymology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D019098:Telomerase; D000099184:Serum-Glucocorticoid Regulated Kinases; C509186:TERT protein, human