Show simple item record

AuthorABDELSALAM, SHAHENDA S.
AuthorPASHA, MAZHAR
AuthorEL-GAMAL, HEBA
AuthorHASAN, MARAM
AuthorELRAYESS, MOHAMED A.
AuthorZEIDAN, ASAD
AuthorKORASHY, HESHAM M.
AuthorAGOUNI, ABDELALI
Available date2023-11-05T07:49:37Z
Publication Date2021-09-01
Publication NameMolecular Medicine Reports
Identifierhttp://dx.doi.org/10.3892/mmr.2021.12304
CitationAbdelsalam, S. S., Pasha, M., El‑Gamal, H., Hasan, M., Elrayess, M. A., Zeidan, A., ... & Agouni, A. (2021). Protein tyrosine phosphatase 1B inhibition improves endoplasmic reticulum stress‑impaired endothelial cell angiogenic response: A critical role for cell survival. Molecular Medicine Reports, 24(3), 1-15.‏
ISSN17912997
URIhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85110934755&origin=inward
URIhttp://hdl.handle.net/10576/49026
AbstractEndoplasmic reticulum (ER) stress contributes to endothelial dysfunction, which is the initial step in atherogenesis. Blockade of protein tyrosine phosphatase (PTP)1B, a negative regulator of insulin receptors that is critically located on the surface of ER membrane, has been found to improve endothelial dysfunction. However, the role of ER stress and its related apoptotic sub-pathways in PTP1B-mediated endothelial dysfunction, particularly its angiogenic capacity, have not yet been fully elucidated. Thus, the present study aimed to investigate the impact of PTP1B suppression on ER stress-mediated impaired angiogenesis and examined the contribution of apoptotic signals in this process. Endothelial cells were exposed to pharmacological ER stressors, including thapsigargin (TG) or 1,4-dithiothreitol (DTT), in the presence or absence of a PTP1B inhibitor or small interfering (si)RNA duplexes. Then, ER stress, angiogenic capacity, cell cycle, apoptosis and the activation of key apoptotic signals were assessed. It was identified that the inhibition of PTP1B prevented ER stress caused by DTT and TG. Moreover, ER stress induction impaired the activation of endothelial nitric oxide synthase (eNOS) and the angiogenic capacity of endothelial cells, while PTP1B inhibition exerted a protective effect. The results demonstrated that blockade or knockdown of PTP1B prevented ER stress-induced apoptosis and cell cycle arrest. This effect was associated with reduced expression levels of caspase-12 and poly (ADP-Ribose) polymerase 1. PTP1B blockade also suppressed autophagy activated by TG. The current data support the critical role of PTP1B in ER stress-mediated endothelial dysfunction, characterized by reduced angiogenic capacity, with an underlying mechanism involving reduced eNOS activation and cell survival. These findings provide evidence of the therapeutic potential of targeting PTP1B in cardiovascular ischemic conditions.
Languageen
PublisherSpandidos publications
SubjectAngiogenesis
Apoptosis
Endoplasmic reticulum stress
Endothelial dysfunction
Protein tyrosine phosphatase 1B
Tyrosine phosphatases
TitleProtein tyrosine phosphatase 1B inhibition improves endoplasmic reticulum stress-impaired endothelial cell angiogenic response: A critical role for cell survival
TypeArticle
Pagination1-15
Issue Number3
Volume Number24
dc.accessType Abstract Only


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record