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. 2022 Nov;49(11):10479-10488.
doi: 10.1007/s11033-022-07916-x. Epub 2022 Sep 20.

Decreased Sirt3 contributes to cyclic production of reactive oxygen species and islet β-cell apoptosis in high glucose conditions

Zhichen Cai #  1 , Shuqing Liu #  1 , Yaxing Nie #  1 , Bingzheng Dong  2 , Chenglin Li  1 , Jinyuan Zhang  1 , Chunya Xia  1 , Lei Du  1 , Xiaoxing Yin  1 , Jianyun Wang  3
Affiliations

Decreased Sirt3 contributes to cyclic production of reactive oxygen species and islet β-cell apoptosis in high glucose conditions

Zhichen Cai et al. Mol Biol Rep. 2022 Nov.

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.

Keywords: Apoptosis; FoxO1; ROS; Sirt3; β-cell.

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References

    1. Tomita T (2016) Apoptosis in pancreatic beta-islet cells in Type 2 diabetes. Bosn J Basic Med Sci 16:162–179 - DOI - PubMed - PMC
    1. Rehman K, Akash MSH (2017) Mechanism of generation of oxidative stress and pathophysiology of Type 2 diabetes mellitus: how are they interlinked? J Cell Biochem 118:3577–3585 - DOI - PubMed
    1. Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, Nogueira-Machado JA (2018) Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis 9:119 - DOI - PubMed - PMC
    1. Green AS, Chen X, Macko AR, Anderson MJ, Kelly AC, Hart NJ, Lynch RM, Limesand SW (2012) Chronic pulsatile hyperglycemia reduces insulin secretion and increases accumulation of reactive oxygen species in fetal sheep islets. J Endocrinol 212:327–342 - DOI - PubMed
    1. Rebelato E, Santos LR, Carpinelli AR, Rorsman P, Abdulkader F (2018) Short-term high glucose culture potentiates pancreatic beta cell function. Sci Rep 8:13061 - DOI - PubMed - PMC

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