PMID- 35192145
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220426
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 40
IP  - 2
DP  - 2022 Apr
TI  - Curcumin Inhibits Cell Damage and Apoptosis Caused by Thapsigargin-Induced 
      Endoplasmic Reticulum Stress Involving the Recovery of Mitochondrial Function 
      Mediated by Mitofusin-2.
PG  - 449-460
LID - 10.1007/s12640-022-00481-y [doi]
AB  - 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-eIF2alpha. Curcumin attenuated TG-induced damage on cell 
      viability and apoptosis and downregulated the protein levels of GRP78, 
      pSer981-PERK, and pSer51-eIF2alpha. 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.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Zhou, He-Yan
AU  - Zhou HY
AD  - Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing 
      Union University, Beijing, 100191, China.
AD  - Institute of Functional Factors and Brain Sciences, Beijing Union University, 
      Beijing, 100023, China.
FAU - Sun, Yu-Ying
AU  - Sun YY
AD  - Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing 
      Union University, Beijing, 100191, China.
AD  - Institute of Functional Factors and Brain Sciences, Beijing Union University, 
      Beijing, 100023, China.
FAU - Chang, Ping
AU  - Chang P
AD  - Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing 
      Union University, Beijing, 100191, China.
AD  - Institute of Functional Factors and Brain Sciences, Beijing Union University, 
      Beijing, 100023, China.
FAU - Huang, Han-Chang
AU  - Huang HC
AUID- ORCID: 0000-0002-3574-5286
AD  - Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing 
      Union University, Beijing, 100191, China. hanchang@buu.edu.cn.
AD  - Institute of Functional Factors and Brain Sciences, Beijing Union University, 
      Beijing, 100023, China. hanchang@buu.edu.cn.
LA  - eng
GR  - JZ10202001/Academic Research Projects of Beijing Union University/
GR  - XP202008/Academic Research Projects of Beijing Union University/
GR  - ZK70202101/Academic Research Projects of Beijing Union University/
PT  - Journal Article
DEP - 20220222
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Reactive Oxygen Species)
RN  - 67526-95-8 (Thapsigargin)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Apoptosis
MH  - *Curcumin/pharmacology
MH  - *Endoplasmic Reticulum Stress
MH  - Eukaryotic Initiation Factor-2/metabolism
MH  - Mitochondria/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Thapsigargin/metabolism/toxicity
OTO - NOTNLM
OT  - Curcumin
OT  - Endoplasmic reticulum stress (ERS)
OT  - Mitochondrial dysfunction
OT  - Mitofusin-2 (Mfn2)
OT  - SH-SY5Y cells
OT  - Thapsigargin
EDAT- 2022/02/23 06:00
MHDA- 2022/04/27 06:00
CRDT- 2022/02/22 12:15
PHST- 2021/11/26 00:00 [received]
PHST- 2022/02/12 00:00 [accepted]
PHST- 2022/01/23 00:00 [revised]
PHST- 2022/02/23 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2022/02/22 12:15 [entrez]
AID - 10.1007/s12640-022-00481-y [pii]
AID - 10.1007/s12640-022-00481-y [doi]
PST - ppublish
SO  - Neurotox Res. 2022 Apr;40(2):449-460. doi: 10.1007/s12640-022-00481-y. Epub 2022 
      Feb 22.