PMID- 38478195
OWN - NLM
STAT- MEDLINE
DCOM- 20240315
LR  - 20240328
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 74
IP  - 1
DP  - 2024 Mar 13
TI  - Effects of the Glucocorticoid-Mediated Mitochondrial Translocation of 
      Glucocorticoid Receptors on Oxidative Stress and Pyroptosis in BV-2 Microglia.
PG  - 30
LID - 10.1007/s12031-024-02192-9 [doi]
AB  - Microglia are resident macrophages within the central nervous system, serving as 
      the first responders to neuroinflammation. Glucocorticoids (GCs) may cause damage 
      to brain tissue, but the specific mechanism remains unclear. This study was 
      divided into two parts: a glucocorticoid receptor (GR) mitochondrial 
      translocation intervention experiment and a mitochondrial oxidative stress 
      inhibition experiment. BV-2 microglia were stimulated with dexamethasone (DEX) 
      and treated with either tubastatin-A or mitoquinone (MitoQ) for 24 h. Our results 
      showed that DEX increased the translocation of GRs to mitochondria, and this 
      effect was accompanied by decreases in the expression of mitochondrially encoded 
      cytochrome c oxidase 1 (MT-CO1) and mitochondrially encoded cytochrome c oxidase 
      3 (MT-CO3) and increases in the expression of NOD-like receptor thermal protein 
      domain-associated protein 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD). The 
      level of mitochondrial respiratory chain complex IV (MRCC IV) and adenosine 
      triphosphate (ATP) was decreased. An elevation in the level of mitochondrial 
      oxidative stress and the opening of the mitochondrial permeability transition 
      pore (mPTP) was also observed. Mechanistically, tubastatin-A significantly 
      suppressed the mitochondrial translocation of GRs, improved the expression of 
      mitochondrial genes, promoted the restoration of mitochondrial function, and 
      inhibited pyroptosis. MitoQ significantly prevented mitochondrial oxidative 
      stress, improved mitochondrial function, and reduced apoptosis and pyroptosis. 
      Both tubastatin-A and MitoQ suppressed DEX-induced pyroptosis. This study 
      substantiates that the increase in the mitochondrial translocation of GRs 
      mediated by GCs exacerbates oxidative stress and pyroptosis in microglia, which 
      indicates that the regulation of mitochondrial pathways by GCs is pathogenic to 
      microglia.
CI  - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Dang, Ruonan
AU  - Dang R
AUID- ORCID: 0000-0002-6168-7315
AD  - Department of Chinese Medicine, School of First Clinical Medicine, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical 
      University, Guangzhou, 510120, China.
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
FAU - Hou, Xuyang
AU  - Hou X
AD  - Department of Chinese Medicine, School of First Clinical Medicine, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical 
      University, Guangzhou, 510120, China.
AD  - Institute of Integration of Traditional and Western Medicine, Guangzhou Medical 
      University, Guangzhou, 510182, China.
FAU - Huang, Xinglan
AU  - Huang X
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Dermatology, Guangzhou Twelfth People's Hospital, Guangzhou, 
      510620, China.
FAU - Huang, Caifeng
AU  - Huang C
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Dermatology, School of First Clinical Medicine, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical 
      University, Guangzhou, 510120, China.
FAU - Zhao, Xiaoqing
AU  - Zhao X
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Endocrinology, The Affiliated TCM Hospital of Guangzhou Medical 
      University, Guangzhou Medical University, Guangzhou, 510130, China.
FAU - Wang, Xingrong
AU  - Wang X
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Dermatology, School of First Clinical Medicine, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical 
      University, Guangzhou, 510120, China.
FAU - Zhang, Ning
AU  - Zhang N
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Dermatology, School of First Clinical Medicine, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical 
      University, Guangzhou, 510120, China.
FAU - Yang, Yuqi
AU  - Yang Y
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Endocrinology, The Affiliated TCM Hospital of Guangzhou Medical 
      University, Guangzhou Medical University, Guangzhou, 510130, China.
FAU - Li, Nan
AU  - Li N
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Dermatology, Haizhu Maternal and Child Health Hospital, Guangzhou, 
      510240, China.
FAU - Liu, Sheng
AU  - Liu S
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Dermatology, School of First Clinical Medicine, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical 
      University, Guangzhou, 510120, China.
FAU - Yan, Peng
AU  - Yan P
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Critical Care Medicine, Guangzhou First People's Hospital, South 
      China University of Technology, Guangzhou, 510180, China.
FAU - Fan, Ping
AU  - Fan P
AD  - Department of Chinese Medicine, School of First Clinical Medicine, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical 
      University, Guangzhou, 510120, China.
AD  - Institute of Integration of Traditional and Western Medicine, Guangzhou Medical 
      University, Guangzhou, 510182, China.
FAU - Song, Xinghua
AU  - Song X
AD  - Department of Chinese Medicine, School of First Clinical Medicine, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical 
      University, Guangzhou, 510120, China.
AD  - Institute of Integration of Traditional and Western Medicine, Guangzhou Medical 
      University, Guangzhou, 510182, China.
FAU - Zhang, Suiying
AU  - Zhang S
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Dermatology, SSL Central Hospital, Southern Medical University, 
      Dongguan, 523888, China.
FAU - Deng, Yuqiong
AU  - Deng Y
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China.
AD  - Department of Dermatology, Panyu Maternal and Child Care Service Centre of 
      Guangzhou, Guangzhou, 511400, China.
FAU - Cheng, Xiping
AU  - Cheng X
AUID- ORCID: 0000-0001-8248-3429
AD  - State Key Laboratory of Respiratory Disease, Guangzhou Medical University, 
      Guangzhou, 510182, China. cxplunwenyx@163.com.
AD  - Department of Dermatology, School of First Clinical Medicine, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical 
      University, Guangzhou, 510120, China. cxplunwenyx@163.com.
FAU - Xia, Xinhua
AU  - Xia X
AD  - Department of Chinese Medicine, School of First Clinical Medicine, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical 
      University, Guangzhou, 510120, China. star1124@163.com.
AD  - Institute of Integration of Traditional and Western Medicine, Guangzhou Medical 
      University, Guangzhou, 510182, China. star1124@163.com.
LA  - eng
GR  - 3208203801/Guangzhou City's Construction Project for Tier-Three Famous 
      Traditional Chinese Medicine Clinics/
GR  - ZNSA-2020013/Zhongnanshan Medical Foundation of Guangdong Province/
GR  - 81673983, 82074172/National Natural Science Foundation of China/
GR  - 02820005/Natural Science Foundation of Guangdong Province/
PT  - Journal Article
DEP - 20240313
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
SB  - IM
MH  - *Glucocorticoids/pharmacology/metabolism
MH  - *Pyroptosis
MH  - Receptors, Glucocorticoid/genetics/metabolism
MH  - Microglia/metabolism
MH  - Electron Transport Complex IV/metabolism
MH  - Oxidative Stress
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
OTO - NOTNLM
OT  - Glucocorticoid
OT  - Glucocorticoid receptor
OT  - Microglia
OT  - Mitochondria oxidative stress
OT  - Neurodegenerative diseases
OT  - Pyroptosis
EDAT- 2024/03/13 18:47
MHDA- 2024/03/15 06:43
CRDT- 2024/03/13 12:21
PHST- 2023/12/13 00:00 [received]
PHST- 2024/01/17 00:00 [accepted]
PHST- 2024/03/15 06:43 [medline]
PHST- 2024/03/13 18:47 [pubmed]
PHST- 2024/03/13 12:21 [entrez]
AID - 10.1007/s12031-024-02192-9 [pii]
AID - 10.1007/s12031-024-02192-9 [doi]
PST - epublish
SO  - J Mol Neurosci. 2024 Mar 13;74(1):30. doi: 10.1007/s12031-024-02192-9.