PMID- 32090372
OWN - NLM
STAT- MEDLINE
DCOM- 20210119
LR  - 20211204
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 34
IP  - 4
DP  - 2020 Apr
TI  - Neuroprotective and vision-protective effect of preserving ATP levels by AMPK 
      activator.
PG  - 5016-5026
LID - 10.1096/fj.201902387RR [doi]
AB  - Progression of blinding diseases, such as age-related macular degeneration, is 
      accelerated by light exposure. However, no particular intervention is applied to 
      the photostress. Here, we report neuroprotective effects of the adenosine 
      monophosphate (AMP)-activated protein kinase (AMPK) activator, 
      5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR), on light-induced visual 
      function impairment, photoreceptor disorders and death in mice. Increase in 
      retinal ATP levels in response to photostress was transient, because oxygen 
      consumption rate (OCR) and cytochrome c oxidase (CcO) activity were reduced under 
      photostress. However, AICAR treatment preserved OCR, CcO activity, and high 
      levels of retinal ATP after light exposure. AMPK knockdown in the 
      photoreceptor-derived cell line revealed that AMPK targeted CcO activity. 
      Further, our data indicated that photostress reduced mitochondrial respiratory 
      function and ATP levels, while AICAR treatment promoted neuronal survival and 
      retained visual function, stabilizing ATP levels through preserved CcO activity. 
      The current study has provided proof of concept for providing cells with 
      sufficient energy to promote cell survival in the presence of cellular stress. 
      This is in contrast to the previous reports which primarily investigated 
      therapeutic approaches to suppress stress signals. Hence, stabilization of the 
      ATP supply may serve as a novel therapeutic approach to support tissue survival 
      under stress and prevent neurodegeneration.
CI  - (c) 2020 The Authors. The FASEB Journal published by Wiley Periodicals, Inc. on 
      behalf of Federation of American Societies for Experimental Biology.
FAU - Kawashima, Hirohiko
AU  - Kawashima H
AD  - Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, 
      Japan.
AD  - Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
FAU - Ozawa, Yoko
AU  - Ozawa Y
AUID- ORCID: 0000-0003-4797-5705
AD  - Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, 
      Japan.
AD  - Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
FAU - Toda, Eriko
AU  - Toda E
AD  - Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, 
      Japan.
FAU - Homma, Kohei
AU  - Homma K
AD  - Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, 
      Japan.
FAU - Osada, Hideto
AU  - Osada H
AD  - Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, 
      Japan.
FAU - Narimatsu, Toshio
AU  - Narimatsu T
AD  - Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, 
      Japan.
AD  - Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
FAU - Nagai, Norihiro
AU  - Nagai N
AD  - Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, 
      Japan.
AD  - Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
FAU - Tsubota, Kazuo
AU  - Tsubota K
AD  - Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200224
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Adenosine Triphosphate/*metabolism
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/pharmacology/therapeutic use
MH  - Animals
MH  - Cell Line
MH  - Electron Transport Complex IV/metabolism
MH  - Macular Degeneration/*drug therapy/etiology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Oxygen Consumption
MH  - Protein Kinases/genetics/*metabolism
MH  - Retina/drug effects/metabolism/radiation effects
MH  - Ribonucleotides/*pharmacology/therapeutic use
MH  - Ultraviolet Rays/adverse effects
OTO - NOTNLM
OT  - AMPK
OT  - ATP
OT  - Neurodegeneration
OT  - photostress
OT  - retina
EDAT- 2020/02/25 06:00
MHDA- 2021/01/20 06:00
CRDT- 2020/02/25 06:00
PHST- 2019/09/17 00:00 [received]
PHST- 2020/01/17 00:00 [revised]
PHST- 2020/01/22 00:00 [accepted]
PHST- 2020/02/25 06:00 [pubmed]
PHST- 2021/01/20 06:00 [medline]
PHST- 2020/02/25 06:00 [entrez]
AID - 10.1096/fj.201902387RR [doi]
PST - ppublish
SO  - FASEB J. 2020 Apr;34(4):5016-5026. doi: 10.1096/fj.201902387RR. Epub 2020 Feb 24.