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  • Title: Decreased Sirt3 contributes to cyclic production of reactive oxygen species and islet β-cell apoptosis in high glucose conditions.
    Author: Cai Z, Liu S, Nie Y, Dong B, Li C, Zhang J, Xia C, Du L, Yin X, Wang J.
    Journal: Mol Biol Rep; 2022 Nov; 49(11):10479-10488. PubMed ID: 36125675.
    Abstract:
    BACKGROUND: Reactive oxygen species (ROS) plays a vital role in the apoptosis of islet β-cells in type 2 diabetes mellitus (T2DM). Sirt3 (Sirtuin 3, a deacetylase) and FoxO1 (a transcription factor) might be involved in ROS production. This study was to investigate mechanism of ROS production and β-cell apoptosis in T2DM. METHODS: Oxidative stress and apoptosis in islets of db/db mice and high glucose cultured β-cells were observed by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay and western blotting. Then, H2O2 was used to ascertain the effect of ROS on the expression of Sirt3. Meanwhile, FoxO1, antioxidant enzymes - catalase (CAT) and manganese superoxide dismutase (MnSOD) and β-cell apoptosis were also determined by western blotting. Finally, Sirt3 was knocked down to evaluate the effect on oxidative stress and apoptosis of β-cells. RESULTS: Under high glucose environment, enhanced ROS made a decrease of Sirt3 expression, which increased acetylation of FoxO1, thus reduced the expression of its target proteins -MnSOD and CAT, and further significantly increased ROS levels. Increased ROS finally led to the apoptosis of β-cells. CONCLUSION: Down-regulation of Sirt3 plays an important role in the cyclic production of ROS and β-cell apoptosis. Targeting Sirt3 may be favorable for the treatment of T2DM.
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