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Mechanisms of β-adrenergic receptors agonists in mediating pro and anti-apoptotic pathways in hyperglycemic Müller cells

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Abstract

Background

The current study aimed to investigate the stimulatory effect of beta-adrenergic receptors (β-ARs) on brain derived neurotropic factor (BDNF) and cAMP response element binding protein (CREB).

Methods

Human Müller cells were cultured in low and high glucose conditions. Cells were treated with xamoterol (selective agonist for β1-AR), salmeterol (selective agonist for β2-AR), isoproterenol (β-ARs agonist) and propranolol (β-ARs antagonist), at 20 µM concentration for 24 h. Western Blotting assay was performed for the gene expression analysis. DNA damage was evaluated by TUNEL assay. DCFH-DA assay was used to check the level of reactive oxygen species (ROS). Cytochrome C release was measured by ELISA.

Results

Xamoterol, salmeterol and isoproterenol showed no effect on Caspase-8 but it reduced the apoptosis and increased the expression of BDNF in Müller cells. A significant change in the expression of caspase-3 was observed in cells treated with xamoterol and salmeterol as compared to isoproterenol. Xamoterol, salmeterol and isoproterenol significantly decreased the reactive oxygen species (ROS) when treated for 24 hours. Glucose-induced cytochrome c release was disrupted in Müller cells.

Conclusion

β-ARs, stimulated by agonist play a protective role in hyperglycemic Müller cells, with the suppression of glucose-induced caspase-3 and cytochrome c release. B-Ars may directly mediate the gene expression of BDNF.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Faculty of Medicine, Bioscience and Nursing, MAHSA University, 42610, Jenjarom, Selangor, Malaysia

    Sher Zaman Safi, Vetriselvan Subramaniyan & Ikram Shah Bin Ismail

  2. IRCBM, COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan

    Sher Zaman Safi

  3. Department of Zoology, Lahore College for Women University, Lahore, Pakistan

    Laiba Saeed

  4. KRSS University of Management and Technology, Lahore, Pakistan

    Humaira Shah

  5. Regional Blood Center Peshawar, Peshawar, Pakistan

    Zahina Latif

  6. Department of Zoology, Abdul Wali Khan University, Mardan, Mardan, Pakistan

    Abid Ali

  7. Department of Microbiology, University of Health Sciences, Lahore, Lahore, Pakistan

    Muhammad Imran & Nawshad Muhammad

  8. Department of Dental Materials, Institute of Basic Medical Sciences, Khyber Medical University Peshawar, Peshawar, Pakistan

    Nawshad Muhammad

  9. Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4381, Bangladesh

    Talha Bin Emran

  10. Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh

    Talha Bin Emran

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  1. Sher Zaman Safi
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All authors contributed to the study conception, design, material preparation, data collection and analysis.

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Correspondence to Sher Zaman Safi.

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Safi, S.Z., Saeed, L., Shah, H. et al. Mechanisms of β-adrenergic receptors agonists in mediating pro and anti-apoptotic pathways in hyperglycemic Müller cells. Mol Biol Rep 49, 9473–9480 (2022). https://doi.org/10.1007/s11033-022-07816-0

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