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Article

Protein tyrosine phosphatase 1B inhibition improves endoplasmic reticulum stress‑impaired endothelial cell angiogenic response: A critical role for cell survival

  • Authors:
    • Shahenda S. Abdelsalam
    • Mazhar Pasha
    • Heba El‑Gamal
    • Maram Hasan
    • Mohamed A. Elrayess
    • Asad Zeidan
    • Hesham M. Korashy
    • Abdelali Agouni
  • View Affiliations / Copyright

    Affiliations: Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, P.O. Box 2713 Doha, Qatar, Biomedical Research Center, Qatar University, P.O. Box 2713 Doha, Qatar, Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, P.O. Box 2713 Doha, Qatar
  • Article Number: 665
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    Published online on: July 20, 2021
       https://doi.org/10.3892/mmr.2021.12304
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Abstract

Endoplasmic 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.
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Spandidos Publications style
Abdelsalam SS, Pasha M, El‑Gamal H, Hasan M, Elrayess MA, Zeidan A, Korashy HM and Agouni A: Protein tyrosine phosphatase 1B inhibition improves endoplasmic reticulum stress‑impaired endothelial cell angiogenic response: A critical role for cell survival. Mol Med Rep 24: 665, 2021.
APA
Abdelsalam, 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, 665. https://doi.org/10.3892/mmr.2021.12304
MLA
Abdelsalam, S. S., Pasha, M., El‑Gamal, H., Hasan, M., Elrayess, M. A., Zeidan, A., Korashy, H. M., Agouni, A."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 (2021): 665.
Chicago
Abdelsalam, S. S., Pasha, M., El‑Gamal, H., Hasan, M., Elrayess, M. A., Zeidan, A., Korashy, H. M., Agouni, A."Protein tyrosine phosphatase 1B inhibition improves endoplasmic reticulum stress‑impaired endothelial cell angiogenic response: A critical role for cell survival". Molecular Medicine Reports 24, no. 3 (2021): 665. https://doi.org/10.3892/mmr.2021.12304
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Spandidos Publications style
Abdelsalam SS, Pasha M, El‑Gamal H, Hasan M, Elrayess MA, Zeidan A, Korashy HM and Agouni A: Protein tyrosine phosphatase 1B inhibition improves endoplasmic reticulum stress‑impaired endothelial cell angiogenic response: A critical role for cell survival. Mol Med Rep 24: 665, 2021.
APA
Abdelsalam, 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, 665. https://doi.org/10.3892/mmr.2021.12304
MLA
Abdelsalam, S. S., Pasha, M., El‑Gamal, H., Hasan, M., Elrayess, M. A., Zeidan, A., Korashy, H. M., Agouni, A."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 (2021): 665.
Chicago
Abdelsalam, S. S., Pasha, M., El‑Gamal, H., Hasan, M., Elrayess, M. A., Zeidan, A., Korashy, H. M., Agouni, A."Protein tyrosine phosphatase 1B inhibition improves endoplasmic reticulum stress‑impaired endothelial cell angiogenic response: A critical role for cell survival". Molecular Medicine Reports 24, no. 3 (2021): 665. https://doi.org/10.3892/mmr.2021.12304
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