PMID- 38049617
OWN - NLM
STAT- MEDLINE
DCOM- 20240202
LR  - 20240202
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 241
IP  - 2
DP  - 2024 Feb
TI  - Insufficient autophagy enables the nuclear factor erythroid 2-related factor 2 
      (NRF2) to promote ferroptosis in morphine-treated SH-SY5Y cells.
PG  - 291-304
LID - 10.1007/s00213-023-06485-6 [doi]
AB  - RATIONALE: While morphine has important therapeutic value it is also one of the 
      most widely abused drugs in the world. As a newly discovered style of cell death, 
      ferroptosis is involved in the occurrence and development of many diseases, 
      however, the current understanding of the relationship between ferroptosis and 
      morphine is still limited. OBJECTIVE: To clarify the role of opioid receptors in 
      morphine-induced ferroptosis and to investigate the role of NRF2 in 
      morphine-induced ferroptosis. METHODS: We first used different doses of morphine 
      (0, 0.5, 1, and 1.5 mM) to investigate morphine-induced ferroptosis in SH-SY5Y 
      cells, and we choose 1.5 mM morphine for subsequent experiments. We next 
      inhibited opioid receptors and NRF2 separately and examined their influence on 
      morphine-induced ferroptosis. Finally, we tested morphine-induced insufficient 
      autophagy. RESULTS: Morphine triggered ferroptosis in a dose-dependent manner, 
      which could be significantly rescued by the ferroptosis-specific inhibitor DFO. 
      Moreover, GPX4 rather than xCT antiporter might be involved in morphine-induced 
      ferroptosis. We also found naloxone could inhibit morphine-induced ferroptosis. 
      Interestingly, our results demonstrated that NRF2 could promote rather than 
      defend morphine-induced ferroptosis; this may be due to the increased p62-related 
      insufficient autophagy. CONCLUSION: Morphine-induced ferroptosis is regulated by 
      the opioid receptor and GPX4 rather than the xCT antiporter. NRF2-mediated 
      ferroptosis in morphine-exposed cells may stem from increased p62-related 
      insufficient autophagy.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Huang, Xin
AU  - Huang X
AUID- ORCID: 0000-0002-2365-677X
AD  - College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, 
      People's Republic of China.
FAU - Yan, Xinyue
AU  - Yan X
AD  - College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, 
      People's Republic of China.
FAU - Chen, Gang
AU  - Chen G
AD  - Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical 
      University, Wenzhou, Zhejiang, 325035, People's Republic of China.
FAU - Feng, Yue
AU  - Feng Y
AD  - College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, 
      People's Republic of China.
FAU - Bai, Yuying
AU  - Bai Y
AD  - College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, 
      People's Republic of China.
FAU - Yan, Peng
AU  - Yan P
AD  - College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, 
      People's Republic of China.
FAU - Lai, Jianghua
AU  - Lai J
AD  - College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, 
      People's Republic of China.
FAU - Wei, Shuguang
AU  - Wei S
AD  - College of Forensic Science, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, 
      People's Republic of China. weisg9676@163.com.
LA  - eng
PT  - Journal Article
DEP - 20231205
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Antiporters)
RN  - 76I7G6D29C (Morphine)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Receptors, Opioid)
RN  - 0 (NFE2L2 protein, human)
SB  - IM
MH  - Humans
MH  - Antiporters
MH  - Autophagy
MH  - *Ferroptosis
MH  - Morphine/pharmacology
MH  - *Neuroblastoma
MH  - NF-E2-Related Factor 2
MH  - Receptors, Opioid
OTO - NOTNLM
OT  - Ferroptosis
OT  - Insufficient autophagy
OT  - Morphine
EDAT- 2023/12/05 00:41
MHDA- 2024/01/24 06:43
CRDT- 2023/12/04 23:38
PHST- 2023/04/23 00:00 [received]
PHST- 2023/10/09 00:00 [accepted]
PHST- 2024/01/24 06:43 [medline]
PHST- 2023/12/05 00:41 [pubmed]
PHST- 2023/12/04 23:38 [entrez]
AID - 10.1007/s00213-023-06485-6 [pii]
AID - 10.1007/s00213-023-06485-6 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2024 Feb;241(2):291-304. doi: 
      10.1007/s00213-023-06485-6. Epub 2023 Dec 5.