Curcumin ameliorates H2O2-induced injury through SIRT1-PERK-CHOP pathway in pancreatic beta cells
ACTA BIOCHIMICA ET BIOPHYSICA SINICA(2022)
Abstract
Oxidative stress and endoplasmic reticulum (ER) stress play crucial roles in pancreatic beta cell destruction, leading to the development and progression of type 1 diabetes mellitus (T1DM). Curcumin, extracted from plant turmeric, possesses multiple bioactivities such as antioxidant, anti-inflammatory and anti-apoptosis properties in vitro and in vivo. However, it remains unknown whether curcumin improves ER stress to prevent beta cells from apoptosis. In this study, we aim to investigate the role and mechanism of curcumin in ameliorating H2O2 -induced injury in MIN6 (a mouse insulinoma cell line) cells. Cell viability is examined by CCK8 assay. Hoechst 33258 staining, TUNEL and flow cytometric assay are performed to detect cell apoptosis. The relative amounts of reactive oxygen species (ROS) are measured by DCFH-DA. WST-8 is used to determine the total superoxide dismutase (SOD) activity. Protein expressions are determined by western blot analysis and immunofluorescence staining. Pretreatment with curcumin prevents MIN6 cells from H2O2-induced cell apoptosis. Curcumin decreases ROS generation and inhibits protein kinase like ER kinase (PERK)-C/EBP homologous protein (CHOP) signaling axis, one of the critical branches of ER stress pathway. Moreover, incubation with curcumin activates silent information regulator 1 (SIRT1) expression and subsequently decreases the expression of CHOP. Additionally, EX527, a specific inhibitor of SIRT1, blocks the protective effect of curcumin on MIN6 cells exposed to H2O2. In sum, curcumin inhibits the PERK-CHOP pathway of ER stress mediated by SIRT1 and thus ameliorates H2O2-induced MIN6 cell apoptosis, suggesting that curcumin and SIRT1 may provide a potential therapeutic approach for T1DM.
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Key words
curcumin, ER stress, SIRT1, apoptosis
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