Sher Zaman Safi1,2, Laiba Saeed3, Humaira Shah4, Zahina Latif5, Abid Ali6, Muhammad Imran7, Nawshad Muhammad7,8, Talha Bin Emran9,10, Vetriselvan Subramaniyan11, Ikram Shah Bin Ismail11. 1. Faculty of Medicine, Bioscience and Nursing, MAHSA University, 42610, Jenjarom, Selangor, Malaysia. safi.nust@yahoo.com. 2. IRCBM, COMSATS University Islamabad, Lahore Campus, Lahore, Pakistan. safi.nust@yahoo.com. 3. Department of Zoology, Lahore College for Women University, Lahore, Pakistan. 4. KRSS University of Management and Technology, Lahore, Pakistan. 5. Regional Blood Center Peshawar, Peshawar, Pakistan. 6. Department of Zoology, Abdul Wali Khan University, Mardan, Mardan, Pakistan. 7. Department of Microbiology, University of Health Sciences, Lahore, Lahore, Pakistan. 8. Department of Dental Materials, Institute of Basic Medical Sciences, Khyber Medical University Peshawar, Peshawar, Pakistan. 9. Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4381, Bangladesh. 10. Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, 1207, Bangladesh. 11. Faculty of Medicine, Bioscience and Nursing, MAHSA University, 42610, Jenjarom, Selangor, Malaysia.
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.
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.
Authors: Paula V Subirada; María C Paz; Magali E Ridano; Valeria E Lorenc; María V Vaglienti; Pablo F Barcelona; José D Luna; María C Sánchez Journal: Eur J Neurosci Date: 2018-06-08 Impact factor: 3.386
Authors: Elena Vecino; F David Rodriguez; Noelia Ruzafa; Xandra Pereiro; Sansar C Sharma Journal: Prog Retin Eye Res Date: 2015-06-23 Impact factor: 21.198
Authors: Francesco Saverio Sorrentino; Michael Allkabes; Giulia Salsini; Claudio Bonifazzi; Paolo Perri Journal: Life Sci Date: 2016-08-03 Impact factor: 5.037
Authors: Ricardo Augusto de Melo Reis; Ana Lúcia Marques Ventura; Clarissa Sampaio Schitine; Maria Christina Fialho de Mello; Fernando Garcia de Mello Journal: Neurochem Res Date: 2008-02-14 Impact factor: 3.996