TY - JOUR
T1 - Mechanisms of β-adrenergic receptors agonists in mediating pro and anti-apoptotic pathways in hyperglycemic Müller cells
AU - Safi, Sher Zaman
AU - Saeed, Laiba
AU - Shah, Humaira
AU - Latif, Zahina
AU - Ali, Abid
AU - Imran, Muhammad
AU - Muhammad, Nawshad
AU - Emran, Talha Bin
AU - Subramaniyan, Vetriselvan
AU - Ismail, Ikram Shah Bin
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature B.V.
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - Caspase 8
KW - Caspase-3
KW - CREB
KW - Cytochrome C
KW - Müller cells
UR - http://www.scopus.com/inward/record.url?scp=85135317885&partnerID=8YFLogxK
U2 - 10.1007/s11033-022-07816-0
DO - 10.1007/s11033-022-07816-0
M3 - Article
C2 - 35925485
AN - SCOPUS:85135317885
SN - 0301-4851
VL - 49
SP - 9473
EP - 9480
JO - Molecular Biology Reports
JF - Molecular Biology Reports
IS - 10
ER -