PMID- 35014081
OWN - NLM
STAT- MEDLINE
DCOM- 20220602
LR  - 20220818
IS  - 1098-2299 (Electronic)
IS  - 0272-4391 (Linking)
VI  - 83
IP  - 3
DP  - 2022 May
TI  - Mitoquinone intravitreal injection ameliorates retinal ischemia-reperfusion 
      injury in rats involving SIRT1/Notch1/NADPH axis.
PG  - 800-810
LID - 10.1002/ddr.21911 [doi]
AB  - Retinal ischemia-reperfusion injury (RIRI) is an important pathological process 
      of many ocular diseases. Mitoquinone (MitoQ), a mitochondrial targeted 
      antioxidant, is a potential compound for therapeutic development of RIRI. This 
      study observed the effect of MitoQ on RIRI, and further explored its possible 
      molecular mechanism. Temporary increase in intraocular pressure was used to 
      establish rat model of RIRI to observe the effect of MitoQ treatment on retinal 
      function, pathological injury, oxidative stress, inflammation and apoptosis. 
      Immunohistochemistry and Western blot were used to detect expressions of cleaved 
      caspase 3, B cell leukemia/lymphoma 2 associated X (Bax), nicotinamide adenine 
      dinucleotide phosphate oxidase (NOX1), NOX4, cleaved-Notch 1, hairy and enhancer 
      of split 1 (Hes1), and sirtuin 1 (SIRT 1) in retina were detected by 
      immunohistochemistry and Western blot. MitoQ treatment significantly improved 
      retinal function and pathological injury, inhibited the over-production of 
      reactive oxygen species, increased the expression of superoxide dismutase 1 (SOD 
      1), suppressed the releases of inflammatory cytokines, and inhibited retinal 
      cells apoptosis. MitoQ also down-regulated the expressions of cleaved caspase 3, 
      Bax, NOX 1, NOX 4, cleaved-Notch 1, and Hes 1, increased the expression of SIRT 1 
      protein and its activity. These effects were significantly reversed by SIRT1 
      inhibitor EX527. Our data suggests that MitoQ, as a potentially effective drug 
      for improving RIRI, may act through the SIRT1/Notch1/NADPH signal axis.
CI  - (c) 2022 Wiley Periodicals, LLC.
FAU - Tang, Dongyong
AU  - Tang D
AD  - Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Liu, Xin
AU  - Liu X
AD  - Department of Ophthalmology, The Second Affiliated Hospital of Guangxi Medical 
      University, Nanning, China.
FAU - Chen, Jun
AU  - Chen J
AUID- ORCID: 0000-0002-6726-1227
AD  - Department of Traditional Chinese Medicine Surgery, Clinical College, Jiangxi 
      University of Chinese Medicine, Nanchang, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220111
PL  - United States
TA  - Drug Dev Res
JT  - Drug development research
JID - 8204468
RN  - 0 (Notch1 protein, rat)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Receptor, Notch1)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
RN  - 53-59-8 (NADP)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.5.1.- (Sirt1 protein, rat)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Caspase 3/metabolism
MH  - Intravitreal Injections
MH  - NADP/metabolism/pharmacology/therapeutic use
MH  - Organophosphorus Compounds
MH  - Oxidative Stress
MH  - Rats
MH  - Receptor, Notch1/metabolism/therapeutic use
MH  - *Reperfusion Injury/metabolism
MH  - Retina/metabolism/pathology
MH  - *Sirtuin 1/metabolism/pharmacology/therapeutic use
MH  - Ubiquinone/analogs & derivatives
MH  - bcl-2-Associated X Protein
OTO - NOTNLM
OT  - Mitoquinone
OT  - ROS
OT  - SIRT 1
OT  - inflammation
OT  - mitochondria injury
OT  - notch 1
OT  - retinal ischemia-reperfusion injury
EDAT- 2022/01/12 06:00
MHDA- 2022/06/03 06:00
CRDT- 2022/01/11 07:04
PHST- 2021/12/14 00:00 [revised]
PHST- 2021/10/15 00:00 [received]
PHST- 2022/01/03 00:00 [accepted]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/06/03 06:00 [medline]
PHST- 2022/01/11 07:04 [entrez]
AID - 10.1002/ddr.21911 [doi]
PST - ppublish
SO  - Drug Dev Res. 2022 May;83(3):800-810. doi: 10.1002/ddr.21911. Epub 2022 Jan 11.