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Acacetin antagonized lipotoxicity in pancreatic β-cells via ameliorating oxidative stress and endoplasmic reticulum stress

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Abstract

Purpose

During the pathogenesis and progression of diabetes, lipotoxicity is a major threat to the function and survival of pancreatic β-cells. To battle against the lipotoxicity induced cellular damages, the present study investigated the beneficial effects of acacetin, a natural antioxidant, on free fatty acid (FFA) stressed RINm5F cells and the potential mechanism involved.

Materials and methods

RINm5F cells with or without 1 h pretreatment of acacetin were treated with 0.35 mM sodium palmitate for 24 h. Cell viability, intracellular reactive oxygen species (ROS) level, antioxidant capacity, cellular apoptosis, and endoplasmic reticulum (ER) stress biomarker expression were investigated.

Results

Our experiments demonstrated that acacetin treatment significantly scavenged the intracellular ROS, upregulated the endogenous antioxidant enzymes, and diminished the sub-G1 DNA fraction in the cells exposed to FFA, suggesting its efficacy against oxidative stress. Meanwhile, acacetin treatment significantly mitigated the overload of intracellular Ca2+ and reduced the pro-apoptotic protein expression in the FFA stimulated cells, and thereby attenuated the ER stress-mediated cell apoptosis. Furthermore, siRNA interference results confirmed that the suppressing of C/EBP-homologous protein (CHOP) was critical to improve FFA-induced reduction in cell viability and ameliorated the ER stress caused by FFA stimulation.

Conclusions

Acacetin may antagonize lipotoxicity in pancreatic cells by attenuating the oxidative stress and ER stress.

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Data availability

All data used in the study are included in the manuscript.

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Acknowledgements

Not applicable.

Funding

This research was approved by the National Natural Science Foundation of China (grant number 81300673), Natural Science Foundation of Jiangsu Province (grant number BK20130496), and Startup Foundation for Advanced Talents of Jiangsu University (grant number 13JDG004 & 13JDG006), Natural Science Foundation of Jiangsu Province (No. BK20191429), and Cultivation Project for Young Core Teacher of Jiangsu University.

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Authors and Affiliations

  1. Department of Biotechnology, School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, Jiangsu, China

    Ning Wang, Qing Gao & Chen Yulan

  2. Department of Biochemistry, School of Medicine, Jiangsu University, Zhenjiang, 212013, Jiangsu, China

    Jie Shi, Weimeng Ji, Xiumei Sheng & Rui Zhang

Authors
  1. Ning Wang
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  2. Qing Gao
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  3. Jie Shi
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  4. Chen Yulan
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  5. Weimeng Ji
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  6. Xiumei Sheng
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  7. Rui Zhang
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Contributions

All authors contributed to the study conception and design. Specifically, material preparation, and data collection were performed by Gao Q, Shi J, Chen YL. Data analysis was conducted by Ji W and Sheng X. Wang N and Zhang R co-supervised the work. Wang N wrote the first draft of manuscript. Zhang R conceived the original experiment design. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ning Wang or Rui Zhang.

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This study complies with all Ethical Standards. The current study does not include any human participants or animals so informed consents are not applicable.

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Wang, N., Gao, Q., Shi, J. et al. Acacetin antagonized lipotoxicity in pancreatic β-cells via ameliorating oxidative stress and endoplasmic reticulum stress. Mol Biol Rep 49, 8727–8740 (2022). https://doi.org/10.1007/s11033-022-07717-2

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