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.

Title

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.

Creator

Harun-Or-Rashid Mohammad; Hallbook Finn

Publisher

Current eye research

Date

2019
2019-01

Description

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

Subject

adrenergic receptors; AKT pathway; and Src-kinase; brimonidine; EGF receptor; ERK1/2; matrix metalloproteinases; Muller cell

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

34–45

Issue

1

Volume

44

Citation

Harun-Or-Rashid Mohammad; Hallbook Finn, “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.,” NEOMED Bibliography Database, accessed November 30, 2021, https://neomed.omeka.net/items/show/4094.

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