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40
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Text
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<a href="http://doi.org/10.1080/02713683.2018.1516783" target="_blank" rel="noreferrer noopener">http://doi.org/10.1080/02713683.2018.1516783</a>
Pages
34–45
Issue
1
Volume
44
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Title
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Alpha 2-Adrenergic Receptor Agonist Brimonidine Stimulates ERK1/2 and AKT Signaling via Transactivation of EGF Receptors in the Human MIO-M1 Muller Cell Line.
Publisher
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Current eye research
Date
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2019
2019-01
Subject
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adrenergic receptors; AKT pathway; and Src-kinase; brimonidine; EGF receptor; ERK1/2; matrix metalloproteinases; Muller cell
Creator
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Harun-Or-Rashid Mohammad; Hallbook Finn
Description
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PURPOSE: Alpha 2-adrenergic receptor (alpha2-ADR) agonists are used clinically for a range of indications including reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Animal experiments show that alpha2-ADR agonists attenuate the injury-induced Muller cell dedifferentiation by a mechanism that involves activation and regulation of extracellular signal-regulated kinase (ERK) 1/2 leading to transactivation of epidermal growth factor receptors (EGFRs). The purpose of this study was to study and corroborate the activation of this system in human cells. MATERIAL AND METHODS: The human Muller cell line MIO-M1 was treated with the alpha2A-ADR agonist brimonidine in combination with inhibitors for Src-kinase, EGFR-kinase, matrix metalloproteinase (MMP) as well as small interfering RNAs (siRNAs) for the EGFR. The cells were analyzed using immunocytochemistry, quantitative PCR and western blot techniques. RESULTS: Our results show that human MIO-M1 cells express alpha2A-ADRs and that stimulation of these receptors caused a robust increase of ERK1/2 and protein kinase B (PKB/AKT) (Thr-308) phosphorylation in
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<a href="http://doi.org/10.1080/02713683.2018.1516783" target="_blank" rel="noreferrer noopener">10.1080/02713683.2018.1516783</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2019
adrenergic receptors
AKT pathway
and Src-kinase
brimonidine
Current eye research
Department of Pharmaceutical Sciences
EGF receptor
ERK1/2
Hallbook Finn
Harun-Or-Rashid Mohammad
matrix metalloproteinases
Muller cell
NEOMED College of Pharmacy