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Isoquercitrin Upregulates Aldolase C Through Nrf2 to Ameliorate OGD/R-Induced Damage in SH-SY5Y Cells

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Abstract

Isoquercitrin (ISO), an extract from Chinese traditional herb, exhibits potent neuroprotective roles in various disease models. However, its role in stroke is not fully understood. We established oxygen–glucose deprivation and reoxygenation (OGD/R) model in SH-SY5Y cell to study the roles of ISO in stroke. In the experiment, the changes of LDH level and cell viability (MTT) were analyzed. Apoptotic cells stained with anti-Annexin V antibody and propidium iodide (PI) were detected by flow cytometry. The mRNA and protein level of aldolase C (ALDOC) and nuclear factor erythroid 2-related factor (Nrf2) was determined by real-time quantitative polymerase chain reaction (qPCR) and Western blotting assay, respectively. The localization of Nrf2 was investigated by immunofluorescent assay. OGD/R reduced cell viability via inducing cell apoptosis, while ISO treatment reduced the level of apoptosis in OGD/R-treated SH-SY5Y cells ISO rescued OGD/R-treated cells. Mechanistically, the expression of Nrf2 and ALDOC was upregulated upon ISO treatment, while knockdown of ALDOC diminished the activation of autophagy and hence inhibited ISO-mediated protective activity. We further demonstrated that ISO enhanced ALDOC transcription by promoting nuclear translocation of Nrf2, and suppression of Nrf2 decreased the expression of ALDOC. Our data revealed that ISO exhibited neuroprotective activity in OGD/R model through Nrf2-ALDOC-autopagy axis and highlighted the potential application of ISO in stroke treatment.

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The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Scientific Research Fund of Hunan Provincial Education Department (No.20A356), the Huaihua Science and Technology Plan (Applied Basic Research) Project (No.2020R3105), and Hunan University of Medicine Scientific Research Incubation Project (No.20200201).

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Authors and Affiliations

  1. Department of Human Anatomy, School of Medicine, Hunan University of Medicine, Huaihua, 418000, Hunan Province, People’s Republic of China

    Shi-Chang Cai, Xiang-Shang Hu & Li-Ming Yi

  2. School of Medicine, Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, Hunan University of Medicine, Huaihua, 418000, Hunan Province, People’s Republic of China

    Shi-Chang Cai & Gen-Yun Tang

  3. Medical Morphology Experimental Center of School of Medicine, Hunan University of Medicine, Huaihua, 418000, Hunan Province, People’s Republic of China

    Chuan-An Yi

  4. School of Public Health and Laboratory Medicine, Hunan University of Medicine, No.492 Jinxi South Road, Hecheng District, Huaihua, 418000, Hunan Province, People’s Republic of China

    Xiu-Ping Li

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  1. Shi-Chang Cai
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Cai, SC., Yi, CA., Hu, XS. et al. Isoquercitrin Upregulates Aldolase C Through Nrf2 to Ameliorate OGD/R-Induced Damage in SH-SY5Y Cells. Neurotox Res 39, 1959–1969 (2021). https://doi.org/10.1007/s12640-021-00430-1

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