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Curcumin Inhibits Cell Damage and Apoptosis Caused by Thapsigargin-Induced Endoplasmic Reticulum Stress Involving the Recovery of Mitochondrial Function Mediated by Mitofusin-2

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Abstract

Endoplasmic reticulum stress (ERS) and mitochondrial dysfunction have been suggested to relate with the pathology of Alzheimer’s disease (AD). However, their cross-talk is needed to investigate further. Mitofusin-2 (Mfn2) is a member of mitochondria-associated membrane (MAM), which connects endoplasmic reticulum (ER) and mitochondria. This study investigated the protective effect of curcumin on thapsigargin (TG)-induced ERS and cell apoptosis and the role of Mfn2 on mitochondrial dysfunction. The cell viability of SH-SY5Y cells was decreased and cell damage and apoptosis were increased in a concentration-dependent manner when cells were treated with TG. TG upregulated the protein levels of GRP78, pSer981-PERK, and pSer51-eIF2α. Curcumin attenuated TG-induced damage on cell viability and apoptosis and downregulated the protein levels of GRP78, pSer981-PERK, and pSer51-eIF2α. TG caused the increases in intracellular reactive oxygen species (ROS) and in the protein levels of pSer40-Nrf2 and hemoglobin oxygenase 1 (HO-1). Curcumin decreased the TG-induced intracellular ROS but did not alter the protein levels of pSer40-Nrf2 and HO-1. TG resulted in the upregulation on Mfn2 expression and mitochondrial spare respiratory capacity but the downregulation on mitochondrial basal respiration and ATP production. Curcumin attenuated the TG-induced Mfn2 expression and mitochondrial stress. When Mfn2 was silenced by shRNA interference, curcumin failed to recovery the TG-damaged mitochondrial function. In general, the TG-induced ERS trigged mitochondrial dysfunction and cell apoptosis. Curcumin attenuates TG-induced ERS and the cell damage and apoptosis. Mfn2 is required for curcumin’s protection against the TG-induced damage on mitochondrial functions.

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Funding

This study was supported by the Academic Research Projects of Beijing Union University (JZ10202001, XP202008, and ZK70202101).

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Authors and Affiliations

  1. Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing, 100191, China

    He-Yan Zhou, Yu-Ying Sun, Ping Chang & Han-Chang Huang

  2. Institute of Functional Factors and Brain Sciences, Beijing Union University, Beijing, 100023, China

    He-Yan Zhou, Yu-Ying Sun, Ping Chang & Han-Chang Huang

Authors
  1. He-Yan Zhou
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  2. Yu-Ying Sun
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  3. Ping Chang
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  4. Han-Chang Huang
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Contributions

Han-Chang Huang: leadership responsibility for the research, design on research goals and methodology, and writing original draft; He-Yan Zhou: conducting investigation process and data curation; Yu-Ying Sun: data validation and statistical analysis and revision on draft. Ping Chang: preparation of study materials, reagents, and materials.

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Correspondence to Han-Chang Huang.

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Zhou, HY., Sun, YY., Chang, P. et al. Curcumin Inhibits Cell Damage and Apoptosis Caused by Thapsigargin-Induced Endoplasmic Reticulum Stress Involving the Recovery of Mitochondrial Function Mediated by Mitofusin-2. Neurotox Res 40, 449–460 (2022). https://doi.org/10.1007/s12640-022-00481-y

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