摘要
衰老是一种以机体稳态逐渐下降为特征的现象。细胞系统不能充分反应应激分子合成等伤害性刺激时产生过早衰老现象。其中,在典型病理生理条件下,血清和糖皮质激素诱导的激酶-1(SGK-1)明显增加,如糖皮质激素或盐皮质激素暴露,炎症,高血糖,和缺血。衰老是一种以机体稳态逐渐下降为特征的现象。细胞系统不能充分反应应激分子合成等伤害性刺激时产生过早衰老现象。其中,在典型病理生理条件下,血清和糖皮质激素诱导的激酶-1(SGK-1)明显增加,如糖皮质激素或盐皮质激素暴露,炎症,高血糖,和缺血。最近,我们证明内皮细胞中SGK-1的活性和表达增加可减少氧化应激现象,提高细胞的存活率和恢复高血糖胰岛素介导的一氧化氮功能。此外,我们表明,SGK-1通过增加端粒酶活性,显著降低活性氧(ROS)的生成,并直接与hTERT相互作用等方式延缓衰老。因此,SGK-1可能代表一个特异性靶点用于进一步开发对某些慢性疾病的新疗法,如以糖尿病为典型的老化。SGK-1也与癌症,神经退行性疾病,心血管疾病,年龄相关的疾病有关联。然而,到目前为止,关于SGK-1和老化可获取的数据很少,也存在争议,仅从线虫的实验模型中得到部分数据。本文试图探讨SGK-1在调节衰老和与年龄有关性疾病的可能机制。此外,本文旨在探讨和确定SGK-1在消除和防止衰老方面发挥的可能的分子靶向作用。
关键词: 衰老,细胞凋亡,肿瘤,炎症,代谢性疾病,氧化应激,SGK-1.。
Current Medicinal Chemistry
Title:Role of Serum and Glucocorticoid-Inducible Kinase (SGK)-1 in Senescence: A Novel Molecular Target Against Age-Related Diseases
Volume: 22 Issue: 33
Author(s): D. Lauro, D. Pastore, B. Capuani, F. Pacifici, R. Palmirotta, P. Abete, M. Roselli, A. Bellia, M. Federici, N. Di Daniele and P. Sbraccia, F. Guadagni, R. Lauro and D. Della-Morte
Affiliation:
关键词: 衰老,细胞凋亡,肿瘤,炎症,代谢性疾病,氧化应激,SGK-1.。
摘要: 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.
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Cite this article as:
D. Lauro, D. Pastore, B. Capuani, F. Pacifici, R. Palmirotta, P. Abete, M. Roselli, A. Bellia, M. Federici, N. Di Daniele and P. Sbraccia, F. Guadagni, R. Lauro and D. Della-Morte , Role of Serum and Glucocorticoid-Inducible Kinase (SGK)-1 in Senescence: A Novel Molecular Target Against Age-Related Diseases, Current Medicinal Chemistry 2015; 22 (33) . https://dx.doi.org/10.2174/0929867322666150812145035
DOI https://dx.doi.org/10.2174/0929867322666150812145035 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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