PMID- 35486208
OWN - NLM
STAT- MEDLINE
DCOM- 20220520
LR  - 20220531
IS  - 1573-7365 (Electronic)
IS  - 0885-7490 (Linking)
VI  - 37
IP  - 5
DP  - 2022 Jun
TI  - RXRgamma attenuates cerebral ischemia-reperfusion induced ferroptosis in neurons in 
      mice through transcriptionally promoting the expression of GPX4.
PG  - 1351-1363
LID - 10.1007/s11011-022-00988-5 [doi]
AB  - Cerebral ischemia is a common cerebrovascular disease with high mortality and 
      disability rate. Exploring its mechanism is essential for developing effective 
      treatment for cerebral ischemia. Therefore, this study aims to explore the 
      regulatory effect and mechanism of retinoid X receptor gamma (RXRgamma) on cerebral 
      ischemia-reperfusion (I/R) injury. A mouse intraluminal middle cerebral artery 
      occlusion model was established, and PC12 cells were exposed to 
      anaerobic/reoxygenation (A/R) as an in vitro model in this study. Cerebral I/R 
      surgery or A/R treatment induced ferroptosis, downregulated RXRgamma and GPX4 
      (glutathione peroxidase 4) levels, upregulated cyclooxygenase-2 (COX-2) level and 
      increased ROS (reactive oxygen species) level in A/R induced cells or I/R brain 
      tissues in vivo or PC12 cells in vitro. Knockdown of RXRgamma downregulated GPX4 and 
      increased COX-2 and ROS levels in A/R induced cells. RXRgamma overexpression has the 
      opposite effect. GPX4 knockdown reversed the improvement of RXRgamma overexpression 
      on COX-2 downregulation, GPX4 upregulation and ferroptosis in PC12 cells. 
      Furthermore, chromatin immunoprecipitation (ChIP) and luciferase reporter gene 
      assays revealed that RXRgamma bound to GPX4 promoter region and activated its 
      transcription. Overexpression of RXRgamma or GPX4 alleviated brain damage and 
      inhibited ferroptosis in I/R mice. In conclusion, RXRgamma-mediated transcriptional 
      activation of GPX4 might inhibit ferroptosis during I/R-induced brain injury.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Yang, Lei
AU  - Yang L
AD  - Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong 
      University, No. 277 Yanta West Road, Yanta District, Xi'an City, Shaanxi 
      Province, 710061, People's Republic of China.
AD  - Department of Neurosurgery, The Second Affiliated Hospital of Xi'an Medical 
      University, Xi'an City, Shaanxi Province, 710038, People's Republic of China.
FAU - Du, Baoshun
AU  - Du B
AD  - Second Department of Neurosurgery, Xinxiang Central Hospital, Xinxiang, Henan 
      Province, 453003, People's Republic of China.
FAU - Zhang, Shitao
AU  - Zhang S
AD  - Department of Neurosurgery, Xi'an No.3 hospital, the Affiliated Hospital of 
      Northwest University, Xi'an City, Shaanxi Province, 710018, People's Republic of 
      China.
FAU - Wang, Maode
AU  - Wang M
AD  - Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong 
      University, No. 277 Yanta West Road, Yanta District, Xi'an City, Shaanxi 
      Province, 710061, People's Republic of China. maode_wang@126.com.
LA  - eng
PT  - Journal Article
DEP - 20220429
PL  - United States
TA  - Metab Brain Dis
JT  - Metabolic brain disease
JID - 8610370
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Retinoid X Receptor gamma)
RN  - EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Animals
MH  - *Brain Ischemia/metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Disease Models, Animal
MH  - *Ferroptosis
MH  - Mice
MH  - Neurons/metabolism
MH  - Phospholipid Hydroperoxide Glutathione Peroxidase
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Reperfusion
MH  - *Reperfusion Injury/metabolism
MH  - Retinoid X Receptor gamma/*metabolism
OTO - NOTNLM
OT  - Ferroptosis
OT  - GPX4
OT  - Ischemia-reperfusion
OT  - Mice
OT  - RXRgamma
EDAT- 2022/04/30 06:00
MHDA- 2022/05/21 06:00
CRDT- 2022/04/29 11:17
PHST- 2022/01/12 00:00 [received]
PHST- 2022/04/17 00:00 [accepted]
PHST- 2022/04/30 06:00 [pubmed]
PHST- 2022/05/21 06:00 [medline]
PHST- 2022/04/29 11:17 [entrez]
AID - 10.1007/s11011-022-00988-5 [pii]
AID - 10.1007/s11011-022-00988-5 [doi]
PST - ppublish
SO  - Metab Brain Dis. 2022 Jun;37(5):1351-1363. doi: 10.1007/s11011-022-00988-5. Epub 
      2022 Apr 29.