期刊
NEUROTOXICITY RESEARCH
卷 40, 期 2, 页码 449-460出版社
SPRINGER
DOI: 10.1007/s12640-022-00481-y
关键词
Curcumin; Endoplasmic reticulum stress (ERS); Mitofusin-2 (Mfn2); Mitochondrial dysfunction; SH-SY5Y cells; Thapsigargin
资金
- Academic Research Projects of Beijing Union University [JZ10202001, XP202008, ZK70202101]
Endoplasmic reticulum stress and mitochondrial dysfunction are related to the pathology of Alzheimer's disease. This study found that curcumin has a protective effect against TG-induced cell damage and apoptosis, and Mfn2 plays a crucial role in the protective mechanism of curcumin.
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-eIF2 alpha. Curcumin attenuated TG-induced damage on cell viability and apoptosis and downregulated the protein levels of GRP78, pSer981-PERK, and pSer51-eIF2 alpha. 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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