Senescence is a phenomenon characterized by a progressive decline of body homeostasis. Premature senescence acts when the cellular system is not able to adequately respond to noxious stimuli by synthesis of stressor molecules. Among those, serum-and-glucocorticoidinducible kinase-1 (SGK-1) dramatically increases under typical physiopathological conditions, such as glucocorticoid or mineralcorticoids exposure, inflammation, hyperglycemia, and ischemia. SGK-1 has been implicated in mechanism regulating oxidative stress, apoptosis, and DNA damage, which are all leading to a state of accelerating aging. Moreover, SGK-1-sensitive ion channels participate in the regulation of renal Na(+)/K(+) regulation, blood pressure, gastric acid secretion, cardiac action potential, and neuroexcitability. Recently, we demonstrated in endothelial cells as an increase in SGK-1 activity and expression reduces oxidative stress, improves cell survival and restores insulin-mediated nitric oxide production after hyperglycemia. Moreover, we showed as SGK-1 delays the onset of senescence by increasing telomerase activity, significantly decreasing reactive oxygen species (ROS) production, and by directly interacting with hTERT. Therefore, SGK-1 may represent a specific target to further develop novel therapeutic options against chronic diseases such as diabetes typical of aging. SGK-1 has been also associated with cancer, neurodegenerative diseases, and cardiovascular disease, among other age-related diseases. However, to date, the data available on SGK-1 and aging, are sparse, controversial, and only from C. elegans experimental models. In this review we sought to discuss the possible implication of SGK-1 in mechanisms regulating senescence and age-related diseases. Moreover, we aimed to discuss and identify the possible role of SGK-1 as possible molecular target to counteract and prevent aging.

Lauro, D., Pastore, D., Capuani, B., Pacifici, F., Palmirotta, R., Abete, P., et al. (2015). Role of serum and glucocorticoid-inducible kinase (SGK)-1 in senescence: a novel molecular target against age-related diseases. CURRENT MEDICINAL CHEMISTRY, 22(33), 3765-3788 [10.2174/0929867322666150812145035].

Role of serum and glucocorticoid-inducible kinase (SGK)-1 in senescence: a novel molecular target against age-related diseases

LAURO, DAVIDE;PASTORE, DONATELLA;CAPUANI, BARBARA;PACIFICI, FABIO;ROSELLI, MARIO;BELLIA, ALFONSO;FEDERICI, MASSIMO;DI DANIELE, NICOLA;SBRACCIA, PAOLO;LAURO, RENATO;DELLA MORTE, DAVID
2015-01-01

Abstract

Senescence is a phenomenon characterized by a progressive decline of body homeostasis. Premature senescence acts when the cellular system is not able to adequately respond to noxious stimuli by synthesis of stressor molecules. Among those, serum-and-glucocorticoidinducible kinase-1 (SGK-1) dramatically increases under typical physiopathological conditions, such as glucocorticoid or mineralcorticoids exposure, inflammation, hyperglycemia, and ischemia. SGK-1 has been implicated in mechanism regulating oxidative stress, apoptosis, and DNA damage, which are all leading to a state of accelerating aging. Moreover, SGK-1-sensitive ion channels participate in the regulation of renal Na(+)/K(+) regulation, blood pressure, gastric acid secretion, cardiac action potential, and neuroexcitability. Recently, we demonstrated in endothelial cells as an increase in SGK-1 activity and expression reduces oxidative stress, improves cell survival and restores insulin-mediated nitric oxide production after hyperglycemia. Moreover, we showed as SGK-1 delays the onset of senescence by increasing telomerase activity, significantly decreasing reactive oxygen species (ROS) production, and by directly interacting with hTERT. Therefore, SGK-1 may represent a specific target to further develop novel therapeutic options against chronic diseases such as diabetes typical of aging. SGK-1 has been also associated with cancer, neurodegenerative diseases, and cardiovascular disease, among other age-related diseases. However, to date, the data available on SGK-1 and aging, are sparse, controversial, and only from C. elegans experimental models. In this review we sought to discuss the possible implication of SGK-1 in mechanisms regulating senescence and age-related diseases. Moreover, we aimed to discuss and identify the possible role of SGK-1 as possible molecular target to counteract and prevent aging.
2015
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/13 - ENDOCRINOLOGIA
Settore MED/09 - MEDICINA INTERNA
Settore MED/06 - ONCOLOGIA MEDICA
English
Con Impact Factor ISI
SGK-1, Insulin, Senescence
Lauro, D., Pastore, D., Capuani, B., Pacifici, F., Palmirotta, R., Abete, P., et al. (2015). Role of serum and glucocorticoid-inducible kinase (SGK)-1 in senescence: a novel molecular target against age-related diseases. CURRENT MEDICINAL CHEMISTRY, 22(33), 3765-3788 [10.2174/0929867322666150812145035].
Lauro, D; Pastore, D; Capuani, B; Pacifici, F; Palmirotta, R; Abete, P; Roselli, M; Bellia, A; Federici, M; DI DANIELE, N; Sbraccia, P; Guadagni, F; Lauro, R; DELLA MORTE, D
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/147727
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