The novel secretome ST266 activates Akt and protects against oxidative stress-mediated injury in human RPE and Müller cells.

Autor: Tang AC; Department of Ophthalmology, Duke University, Durham, NC, 27710, USA., Besley NA; Department of Ophthalmology, Duke University, Durham, NC, 27710, USA., Trimpey-Warfhatig R; Department of Ophthalmology, Duke University, Durham, NC, 27710, USA., Yang P; Department of Ophthalmology, Duke University, Durham, NC, 27710, USA., Wessel H; Noveome Biotherapeutics, Inc., Pittsburgh, PA, 27708, USA., Brown L; Noveome Biotherapeutics, Inc., Pittsburgh, PA, 27708, USA., Kirshner Z; Noveome Biotherapeutics, Inc., Pittsburgh, PA, 27708, USA., Jaffe GJ; Noveome Biotherapeutics, Inc., Pittsburgh, PA, 27708, USA. Electronic address: jaffe001@mc.duke.edu.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2024 Nov; Vol. 248, pp. 110060. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1016/j.exer.2024.110060
Abstrakt: Oxidative stress-mediated retinal pigment epithelial (RPE) cell damage is associated with age-related macular degeneration (AMD). ST266 is the biological secretome produced by a novel population of amnion-derived multipotent progenitor cells. Herein, we investigated the effect of ST266 on RPE cell injury induced by hydroquinone (HQ), a cigarette smoke related oxidant, hydrogen peroxide (H 2 O 2 ) and all-trans retinal (atRal), a pro-oxidant component of the retinoid cycle. We additionally investigated its effect on Müller cell injury induced by H 2 O 2 . Cultured human RPE cells were pre-treated for 1 h in the presence or absence of MK-2206, a protein kinase B (Akt) inhibitor, then treated with varying concentrations of HQ, H 2 O 2, or atRal for 1.5 h. Cultured human Müller cells (MIO-M1) were pre-treated for 1 h in the presence or absence of MK-2206, then treated with varying concentrations of H 2 O 2 for 1.5 h. Media were then replaced with STM100 (control media into which the ST266 secretome proteins were collected) or ST266 at various times. Cell viability was determined with WST-1 reagent. Mitochondrial membrane potential (Δψm) was quantified by a fluorescence plate reader. The protein phosphorylation levels of Akt, glycogen synthase kinase 3 beta (GSK-3β), and p70 ribosomal S6 kinase (p70S6K) were measured by Western blot. ST266 significantly improved RPE and MIO-M1 cell viability that was reduced by oxidant exposure and improved oxidant-disrupted Δψm. In both cell types, ST266 induced phosphorylation of Akt, GSK-3β, and p70S6K. MK-2206 significantly eliminated ST266-mediated protein phosphorylation of Akt, GSK-3β, and p70S6K and abolished the ST266-protective effect on cell viability. In conclusion, ST266 activates Akt, protects against oxidative stress-mediated cell injury in an Akt-dependent manner, and improves Δψm, suggesting a potential role for ST266 therapy in treating retinal diseases such as AMD.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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