In:
Acta Ophthalmologica, Wiley, Vol. 100, No. S275 ( 2022-12)
Kurzfassung:
References: Antioxidant systems are essential in many elderly diseases, including age‐related macular degeneration (AMD). Oxidative stress, inflammation, protein degradation impairment, are well‐described in AMD retinal pigment epithelial (RPE) cells. Nrf2 (NF‐E2‐related factor 2), master regulator of antioxidant defence, is linked to AMD, autophagy, inflammation. We previously showed that nature‐inspired hybrids (NIH1‐3) induce Nrf2‐mediated protection against AMD‐related pro‐oxidant stimuli in RPE cells. Purpose: In human RPE cells we aimed to further investigate NIH1‐3 for capability to modulate Nrf2 pathway and provide cytoprotection against stress caused by dysfunction of protein homeostasis. Methods: ARPE‐19 cells were treated with 5 μM NIH 1–3, NIH4 (the derivative unable to activate Nrf2) or vehicle (dimethyl sulfoxide; control) for a minimum of 3 h. Proteasome inhibitor MG‐132 (5 μM) and autophagy inhibitor Bafilomycin‐A1 (50 nM) were added after 24 h NIH pre‐treatment. Levels of Nrf2, its target HO‐1 and SQSTM1/p62, the autophagy flux marker LC3‐II, were analysed by Western blotting, whilst IL‐8 release by ELISA, respectively. Cell survival was also assessed. Results: NIH1‐3 activate Nrf2‐pathway and increase HO‐1 and SQSTM1/p62 expression, in turn exerting beneficial effects on intracellular redox balance, without modification of the autophagy flux. NIH1‐3 treatments predispose ARPE‐19 cells to a better response to the following exposure to proteasome and autophagy inhibitors, as revealed by the higher cell survival and decreased secretion of the pro‐inflammatory IL‐8 compared to NIH‐untreated cells. Interestingly, also NIH4 compound, through an Nrf2‐independent pathway, exerts pro‐survival and anti‐inflammatory effects, although to a less extent than NIH1‐3. Conclusions: Our findings suggest that all NIHs are interesting for their cytoprotective properties and confirm Nrf2 as a valuable pharmacological target in contexts characterized by oxidative stress.
Materialart:
Online-Ressource
ISSN:
1755-375X
,
1755-3768
DOI:
10.1111/aos.v100.s275
DOI:
10.1111/j.1755-3768.2022.0261
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2022
ZDB Id:
2466981-7
