Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress
<p dir="ltr">Endoplasmic reticulum (ER) stress is an inflammatory response that contributes to endothelial cell dysfunction, a hallmark of cardiovascular diseases, in close interplay with oxidative stress. Recently, Sestrin2 (SESN2) emerged as a novel stress-inducible protein protect...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , |
| منشور في: |
2021
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| الموضوعات: | |
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| _version_ | 1864513546415505408 |
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| author | Munazza T. Fatima (17280679) |
| author2 | Maram Hasan (6672440) Shahenda S. Abdelsalam (17280682) Siveen K. Sivaraman (17280685) Heba El-Gamal (17280688) Muhammad A. Zahid (17280691) Mohamed A. Elrayess (7956179) Hesham M. Korashy (1474849) Asad Zeidan (8879705) Aijaz S. Parray (15010161) Abdelali Agouni (181926) |
| author2_role | author author author author author author author author author author |
| author_facet | Munazza T. Fatima (17280679) Maram Hasan (6672440) Shahenda S. Abdelsalam (17280682) Siveen K. Sivaraman (17280685) Heba El-Gamal (17280688) Muhammad A. Zahid (17280691) Mohamed A. Elrayess (7956179) Hesham M. Korashy (1474849) Asad Zeidan (8879705) Aijaz S. Parray (15010161) Abdelali Agouni (181926) |
| author_role | author |
| dc.creator.none.fl_str_mv | Munazza T. Fatima (17280679) Maram Hasan (6672440) Shahenda S. Abdelsalam (17280682) Siveen K. Sivaraman (17280685) Heba El-Gamal (17280688) Muhammad A. Zahid (17280691) Mohamed A. Elrayess (7956179) Hesham M. Korashy (1474849) Asad Zeidan (8879705) Aijaz S. Parray (15010161) Abdelali Agouni (181926) |
| dc.date.none.fl_str_mv | 2021-09-15T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.ejphar.2021.174247 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Sestrin2_suppression_aggravates_oxidative_stress_and_apoptosis_in_endothelial_cells_subjected_to_pharmacologically_induced_endoplasmic_reticulum_stress/24433237 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Cardiovascular medicine and haematology Pharmacology and pharmaceutical sciences Cardiovascular disease Endothelial dysfunction Sestrin2 Endoplasmic reticulum (ER) stress Oxidative stress Cell survival |
| dc.title.none.fl_str_mv | Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Endoplasmic reticulum (ER) stress is an inflammatory response that contributes to endothelial cell 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.</p><h2>Other Information</h2><p dir="ltr">Published in: European Journal of Pharmacology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.ejphar.2021.174247" target="_blank">https://dx.doi.org/10.1016/j.ejphar.2021.174247</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_63f9490bfcf1a3fa33d74924e5a0956d |
| identifier_str_mv | 10.1016/j.ejphar.2021.174247 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24433237 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stressMunazza T. Fatima (17280679)Maram Hasan (6672440)Shahenda S. Abdelsalam (17280682)Siveen K. Sivaraman (17280685)Heba El-Gamal (17280688)Muhammad A. Zahid (17280691)Mohamed A. Elrayess (7956179)Hesham M. Korashy (1474849)Asad Zeidan (8879705)Aijaz S. Parray (15010161)Abdelali Agouni (181926)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesCardiovascular medicine and haematologyPharmacology and pharmaceutical sciencesCardiovascular diseaseEndothelial dysfunctionSestrin2Endoplasmic reticulum (ER) stressOxidative stressCell survival<p dir="ltr">Endoplasmic reticulum (ER) stress is an inflammatory response that contributes to endothelial cell 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.</p><h2>Other Information</h2><p dir="ltr">Published in: European Journal of Pharmacology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.ejphar.2021.174247" target="_blank">https://dx.doi.org/10.1016/j.ejphar.2021.174247</a></p>2021-09-15T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.ejphar.2021.174247https://figshare.com/articles/journal_contribution/Sestrin2_suppression_aggravates_oxidative_stress_and_apoptosis_in_endothelial_cells_subjected_to_pharmacologically_induced_endoplasmic_reticulum_stress/24433237CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/244332372021-09-15T00:00:00Z |
| spellingShingle | Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress Munazza T. Fatima (17280679) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Cardiovascular medicine and haematology Pharmacology and pharmaceutical sciences Cardiovascular disease Endothelial dysfunction Sestrin2 Endoplasmic reticulum (ER) stress Oxidative stress Cell survival |
| status_str | publishedVersion |
| title | Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress |
| title_full | Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress |
| title_fullStr | Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress |
| title_full_unstemmed | Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress |
| title_short | Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress |
| title_sort | Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Cardiovascular medicine and haematology Pharmacology and pharmaceutical sciences Cardiovascular disease Endothelial dysfunction Sestrin2 Endoplasmic reticulum (ER) stress Oxidative stress Cell survival |