PMID- 33357768
OWN - NLM
STAT- MEDLINE
DCOM- 20210513
LR  - 20210513
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 145
IP  - 1
DP  - 2021 Jan
TI  - MitoQ protects against high glucose-induced brain microvascular endothelial cells 
      injury via the Nrf2/HO-1 pathway.
PG  - 105-114
LID - S1347-8613(20)30105-5 [pii]
LID - 10.1016/j.jphs.2020.10.007 [doi]
AB  - Brain microvascular endothelial cells (BMECs) dysfunction is related to the 
      pathogenesis of neurovascular complication of diabetes mellitus that adversely 
      lead to various CNS disorders. Mitoquinone (MitoQ) is a mitochondria targeted 
      antioxidant that exerts multiple protective effects in many oxidative 
      damage-related diseases. In this study, we determined the protective effects of 
      MitoQ on high glucose (HG)-induced BMECs injury and investigated the underlying 
      mechanism. We found that HG significantly reduced the expression of Nrf2 and 
      HO-1, decreased mitochondrial membrane potential, increased intracellular and 
      mitochondrial reactive oxygen species (ROS) generation, induced cytoskeletal 
      damage and apoptosis in BMECs. In addition, Mito tempol, a mitochondrial ROS 
      scavenger, significantly reduced HG-induced mitochondrial ROS production and 
      attenuated cytoskeletal damage and cell apoptosis, suggesting MtROS production 
      was involved in HG-induced BMECs injury. Moreover, we found that MitoQ treatment 
      significantly upregulated the expression of Nrf2 and HO-1 in HG-induced BMECs, 
      which is accompanied by improved mitochondrial membrane potential and decreased 
      MtROS production. Meanwhile, MitoQ treatment also remarkably attenuated 
      HG-induced cytoskeletal damage and cell apoptosis in BMECs. However, inhibitor of 
      Nrf2 with ML385 impaired the protective effects of MitoQ in HG-induced BMECs. In 
      conclusion, our results suggest that MitoQ exerts protective effect on HG-induced 
      BMECs injury via activating Nrf2/HO-1 pathway.
CI  - Copyright (c) 2020 The Authors. Production and hosting by Elsevier B.V. All rights 
      reserved.
FAU - Yang, Min-Yan
AU  - Yang MY
AD  - Department of Internal Medicine, The Fourth People's Hospital of Chengdu, 
      Chengdu, Sichuan, China.
FAU - Fan, Zhen
AU  - Fan Z
AD  - Department of Geriatrics, Sichuan Academy of Medical Sciences & Sichuan 
      Provincial People's Hospital, Chengdu, Sichuan, China.
FAU - Zhang, Zhao
AU  - Zhang Z
AD  - Department of Emergency, Sichuan Academy of Medical Sciences & Sichuan Provincial 
      People's Hospital, Chengdu, Sichuan, China.
FAU - Fan, Jin
AU  - Fan J
AD  - Department of Neurology, The General Hospital of Western Theater Command, Chendu, 
      Sichuan, China. Electronic address: JinFan5918@163.com.
LA  - eng
PT  - Journal Article
DEP - 20201030
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (Antioxidants)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Reactive Oxygen Species)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (Hmox1 protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Antioxidants
MH  - Apoptosis/drug effects
MH  - Brain/*cytology
MH  - Cells, Cultured
MH  - Endothelial Cells/*metabolism/*pathology
MH  - Glucose/adverse effects
MH  - Heme Oxygenase-1/*metabolism
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - Mitochondria/metabolism
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Organophosphorus Compounds/*pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*drug effects/*genetics
MH  - Ubiquinone/*analogs & derivatives/pharmacology
OTO - NOTNLM
OT  - Brain microvascular endothelial cells
OT  - Diabetes
OT  - MitoQ
OT  - Mitochondrial ROS
OT  - Nrf2
COIS- Declaration of competing interest The authors declare no competing interests 
      relevant to this work.
EDAT- 2020/12/29 06:00
MHDA- 2021/05/14 06:00
CRDT- 2020/12/28 10:25
PHST- 2020/07/10 00:00 [received]
PHST- 2020/10/07 00:00 [revised]
PHST- 2020/10/23 00:00 [accepted]
PHST- 2020/12/28 10:25 [entrez]
PHST- 2020/12/29 06:00 [pubmed]
PHST- 2021/05/14 06:00 [medline]
AID - S1347-8613(20)30105-5 [pii]
AID - 10.1016/j.jphs.2020.10.007 [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2021 Jan;145(1):105-114. doi: 10.1016/j.jphs.2020.10.007. Epub 
      2020 Oct 30.