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المؤلفFatima, Munazza T
المؤلفHasan, Maram
المؤلفAbdelsalam, Shahenda S
المؤلفSivaraman, Siveen K
المؤلفEl-Gamal, Heba
المؤلفZahid, Muhammad A
المؤلفElrayess, Mohamed A
المؤلفKorashy, Hesham M
المؤلفZeidan, Asad
المؤلفParray, Aijaz S
المؤلفAgouni, Abdelali
تاريخ الإتاحة2021-06-16T07:09:36Z
تاريخ النشر2021-06-08
اسم المنشورEuropean Journal of Pharmacology
المعرّفhttp://dx.doi.org/10.1016/j.ejphar.2021.174247
الاقتباسEuropean Journal of Pharmacology Volume 907, 15 September 2021, 174247
معرّف المصادر الموحدhttp://hdl.handle.net/10576/20676
الملخصEndoplasmic reticulum (ER) stress is an inflammatory response that contributes to endothelial dysfunction, a hallmark of cardiovascular diseases, in close interplay with oxidative stress. Recently, Sestrin2 (SESN2) emerged as a novel stress-inducible protein protecting cells from oxidative stress. We investigated here, for the first time, the impact of SESN2 suppression on oxidative stress and cell survival in human endothelial cells subjected to pharmacologically (thapsigargin)-induced ER stress and studied the underlying cellular pathways. We found that SESN2 silencing, though did not specifically induce ER stress, it aggravated the effects of thapsigargin-induced ER stress on oxidative stress and cell survival. This was associated with a dysregulation of Nrf-2, AMPK and mTORC1 signaling pathways. Furthermore, SESN2 silencing aggravated, in an additive manner, apoptosis caused by thapsigargin. Importantly, SESN2 silencing, unlike thapsigargin, caused a dramatic decrease in protein expression and phosphorylation of Akt, a critical pro-survival hub and component of the AMPK/Akt/mTORC1 axis. Our findings suggest that patients with conditions characterized by ER stress activation, such as diabetes, may be at higher risk for cardiovascular complications if their endogenous ability to stimulate and/or maintain expression levels of SESN2 is disturbed or impaired. Therefore, identifying novel or repurposing existing pharmacotherapies to enhance and/or maintain SESN2 expression levels would be beneficial in these conditions.
اللغةen
الناشرElsevier
الموضوعCardiovascular disease
Sestrin2
cell survival
endoplasmic reticulum (ER) stress
endothelial dysfunction
oxidative stress
العنوانSestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress
النوعArticle
رقم المجلد907
dc.accessType Open Access


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