Serum- and Glucocorticoid-Inducible Kinase 1 Delay the Onset of Endothelial Senescence by Directly Interacting with Human Telomerase Reverse Transcriptase

Katia Basello, Francesca Pacifici, Barbara Capuani, Donatella Pastore, Marco F. Lombardo, Francesca Ferrelli, Andrea Coppola, Giulia Donadel, Roberto Arriga, Giuseppe Sconocchia, Alfonso Bellia, Paola Rogliani, Massimo Federici, Paolo Sbraccia, Davide Lauro, David Della Morte

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)79-89
Number of pages11
JournalRejuvenation Research
Volume19
Issue number1
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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    Basello, K., Pacifici, F., Capuani, B., Pastore, D., Lombardo, M. F., Ferrelli, F., Coppola, A., Donadel, G., Arriga, R., Sconocchia, G., Bellia, A., Rogliani, P., Federici, M., Sbraccia, P., Lauro, D., & Della Morte, D. (2016). Serum- and Glucocorticoid-Inducible Kinase 1 Delay the Onset of Endothelial Senescence by Directly Interacting with Human Telomerase Reverse Transcriptase. Rejuvenation Research, 19(1), 79-89. https://doi.org/10.1089/rej.2015.1726