Neuroprotective effects of an Nrf2 agonist on high glucose-induced damage in HT22 cells
2019
Jiangpei Zhao | Lerong Liu | Xia Li | Lingxiao Zhang | Jing Lv | Xueli Guo | Hui Chen | Tongfeng Zhao
Abstract Background Oxidative stress is the hallmark of diabetic encephalopathy, which may be caused by hyperglycaemic toxicity. We aimed to discover pharmacologic targets to restore redox homeostasis. We identified the transcription factor Nrf2 as such a target. Methods HT22 cells were cultured in 25 or 50 mM d-glucose with various concentrations of sulforaphane (SFN) (from 1.25 to 5.0 μM). Cell viability was tested with the Cell Counting Kit-8 assay. Reactive oxygen species (ROS) production was detected with an inverted fluorescence microscope using the dichlorodihydrofluorescein-diacetate fluorescent probe. The expression of NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1) and nuclear factor-κB (NF-κB) at the mRNA and protein levels was detected by reverse transcription quantitative polymerase chain reaction and western blotting. Result We found that a high glucose concentration (50 mM) increased the generation of ROS, downregulated the expression of Nrf2/HO-1 and upregulated the expression of NF-κB. Moreover, HT22 cell viability significantly decreased after culture in high-glucose medium for 24, 48 and 72 h, whereas the activation of the Nrf2/HO-1 pathway using a pharmacological Nrf2 activator abrogated this high-glucose-induced toxicity. Conclusion This study suggests that the activation of the Nrf2–ARE signalling pathway might be a therapeutic target for the treatment of diabetic encephalopathy.
Show more [+] Less [-]AGROVOC Keywords
Bibliographic information
This bibliographic record has been provided by Directory of Open Access Journals
