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AuthorFatima, Munazza T
AuthorHasan, Maram
AuthorAbdelsalam, Shahenda S
AuthorSivaraman, Siveen K
AuthorEl-Gamal, Heba
AuthorZahid, Muhammad A
AuthorElrayess, Mohamed A
AuthorKorashy, Hesham M
AuthorZeidan, Asad
AuthorParray, Aijaz S
AuthorAgouni, Abdelali
Available date2021-06-16T07:09:36Z
Publication Date2021-06-08
Publication NameEuropean Journal of Pharmacology
Identifierhttp://dx.doi.org/10.1016/j.ejphar.2021.174247
CitationEuropean Journal of Pharmacology Volume 907, 15 September 2021, 174247
URIhttp://hdl.handle.net/10576/20676
AbstractEndoplasmic 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.
Languageen
PublisherElsevier
SubjectCardiovascular disease
Sestrin2
cell survival
endoplasmic reticulum (ER) stress
endothelial dysfunction
oxidative stress
TitleSestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress
TypeArticle
Volume Number907
dc.accessType Open Access


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