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Abstract #79948 Published in IGR 20-2

SIRT6 protects retinal ganglion cells against hydrogen peroxide-induced apoptosis and oxidative stress by promoting Nrf2/ARE signaling via inhibition of Bach1

Yu J; Sun W; Song Y; Liu J; Xue F; Gong K; Yang X; Kang Q
Chemico-biological interactions 2019; 300: 151-158

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Oxidative stress-induced damage of retinal ganglion cells (RGCs) is a major contributor to retinal degenerative diseases, such as glaucoma. Sirtuin 6 (SIRT6) has emerged as a cytoprotective protein against various insults. However, whether SIRT6 exerts a protective effect against oxidative stress-damaged RGCs remains unknown. In this study, we aimed to investigate the potential role and regulatory mechanism of SIRT6 in hydrogen peroxide (HO)-induced oxidative damage of RGCs in vitro. We found that SIRT6 expression was significantly downregulated in RGCs with HO treatment. Functional experiments showed that overexpression of SIRT6 improved survival and reduced apoptosis and the production of reactive oxygen species (ROS) in HO-treated RGCs. In contrast, SIRT6 knockdown had the opposite effect. Moreover, we found that SIRT6 overexpression promoted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the activity of antioxidant response element (ARE). In addition, we found that the promotional effect of SIRT6 on Nrf2/ARE signaling was associated with inhibition of BTB and CNC homology 1 (Bach1), an inhibitor of Nrf2. However, overexpression of Bach1 or inhibition of Nrf2/ARE signaling partially reversed the SIRT6-mediated protective effect. Taken together, these results demonstrate that SIRT6 protects RGCs from oxidative stress-induced damage by promoting the activation of Nrf2/ARE signaling via inhibition of Bach1, suggesting a potential role of SIRT6 in retinal degenerative diseases.

Department of Ophthalmology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Department of Ophthalmology, Xi'an No.4 Hospital, Xi'an, 710004, China.

Full article

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Classification:

3.8 Pharmacology (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)

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