The role of SIRT1 on the crosstalk of p65 and NFATS in U937 monocytes under hyperosmotic stress
Soysal, Duygu (2014) The role of SIRT1 on the crosstalk of p65 and NFATS in U937 monocytes under hyperosmotic stress. [Thesis]
Hyperosmotic stress is the increase in whole extracellular solute concentration in cell causing many disruption that may lead to the physiological disease conditions such as diabetes and hypertension. In order to protect itself cells generated an osmotic stress adaptive mechanism in which intracellular inorganic ion homeostasis is restored by mainly activating NFAT5 (TonEBP) and in return it transactivates the target genes or interact with specific regulatory proteins. NFAT5 and p65 have been previously shown to interact at IκB α promoter for regulation of NFκB pathway. In addition to the interaction between NFAT5 and p65, it has been also shown that SIRT1 deacetylates p65 and inhibits its nuclear translocation. However, there is no such study that examines the expression profile of SIRT1, NFAT5 and p65 all together under hyperosmotic stress in U937 cells. Therefore, the aim of this study is to investigate the role of SIRT1 activity on NFAT5 and p65 expression profile under 100mM NaCl induced hyperosmotic stress in U937 monocyte cells. In addition, the aim concerns to understand the scale of contribution of NFAT5 and p65 on NFκB pathway regulation for the cell survival/death under hyperosmotic stress through examining IκB α expression profile. 100mM NaCl induced hyperosmotic stress in U937 monocyte cells indicated high expression levels of NFAT5 and SIRT1 overlapping with the activation of NFκB pathway. It is shown that in U937 cells under 100mM NaCl induced hyperosmotic stress, the activation of NFκB pathway and its regulation may be independent of NFAT5 but highly dependent on translocated p65, and SIRT1 activity may control p65 nuclear translocation, hence NFκB pathway activation.
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