PMID- 33774866
OWN - NLM
STAT- MEDLINE
DCOM- 20210719
LR  - 20210719
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 35
IP  - 5
DP  - 2021 May
TI  - TUFM is involved in Alzheimer's disease-like pathologies that are associated with 
      ROS.
PG  - e21445
LID - 10.1096/fj.202002461R [doi]
AB  - Mitochondrial Tu translation elongation factor (TUFM or EF-Tu) is part of the 
      mitochondrial translation machinery. It is reported that TUFM expression is 
      reduced in the brain of Alzheimer's disease (AD), suggesting that TUFM might play 
      a role in the pathophysiology. In this study, we found that TUFM protein level 
      was decreased in the hippocampus and cortex especially in the aged APP/PS1 mice, 
      an animal model of AD. In HEK cells that stably express full-length human 
      amyloid-beta precursor protein (HEK-APP), TUFM knockdown or overexpression increased 
      or reduced the protein levels of beta-amyloid protein (Abeta) and beta-amyloid converting 
      enzyme 1 (BACE1), respectively. TUFM-mediated reduction of BACE1 was attenuated 
      by translation inhibitor cycloheximide (CHX) or 
      alpha-[2-[4-(3,4-Dichlorophenyl)-2-thiazolyl]hydrazinylidene]-2-nitro-benzenepropanoic 
      acid (4EGI1), and in cells overexpressing BACE1 constructs deleting the 5' 
      untranslated region (5'UTR). TUFM silencing increased the half-life of BACE1 
      mRNA, suggesting that RNA stability was affected by TUFM. In support, 
      transcription inhibitor Actinomycin D (ActD) and silencing of nuclear factor kappaB 
      (NFkappaB) failed to abolish TUFM-mediated regulation of BACE1 protein and mRNA. We 
      further found that the mitochondria-targeted antioxidant TEMPO diminished the 
      effects of TUFM on BACE1, suggesting that reactive oxygen species (ROS) played an 
      important role. Indeed, cellular ROS levels were affected by TUFM knockdown or 
      overexpression, and TUFM-mediated regulation of apoptosis and Tau phosphorylation 
      at selective sites was attenuated by TEMPO. Collectively, TUFM protein levels 
      were decreased in APP/PS1 mice. TUFM is involved in AD pathology by regulating 
      BACE1 translation, apoptosis, and Tau phosphorylation, in which ROS plays an 
      important role.
CI  - (c) 2021 Federation of American Societies for Experimental Biology.
FAU - Zhong, Bi-Rou
AU  - Zhong BR
AD  - Department of Neurology, the First Affiliated Hospital of Chongqing Medical 
      University, Chongqing Key Laboratory of Neurology, Chongqing, China.
FAU - Zhou, Gui-Feng
AU  - Zhou GF
AD  - Department of Neurology, the First Affiliated Hospital of Chongqing Medical 
      University, Chongqing Key Laboratory of Neurology, Chongqing, China.
FAU - Song, Li
AU  - Song L
AD  - Department of Neurology, the First Affiliated Hospital of Chongqing Medical 
      University, Chongqing Key Laboratory of Neurology, Chongqing, China.
FAU - Wen, Qi-Xin
AU  - Wen QX
AD  - Department of Neurology, the First Affiliated Hospital of Chongqing Medical 
      University, Chongqing Key Laboratory of Neurology, Chongqing, China.
FAU - Deng, Xiao-Juan
AU  - Deng XJ
AD  - Department of Neurology, the First Affiliated Hospital of Chongqing Medical 
      University, Chongqing Key Laboratory of Neurology, Chongqing, China.
FAU - Ma, Yuan-Lin
AU  - Ma YL
AD  - Department of Neurology, the First Affiliated Hospital of Chongqing Medical 
      University, Chongqing Key Laboratory of Neurology, Chongqing, China.
FAU - Hu, Li-Tian
AU  - Hu LT
AD  - Department of Neurology, the First Affiliated Hospital of Chongqing Medical 
      University, Chongqing Key Laboratory of Neurology, Chongqing, China.
AD  - Department of Neurology, Nanchong Central Hospital, the Second Clinical College 
      of North Sichuan Medical College, Nanchong, China.
FAU - Chen, Guo-Jun
AU  - Chen GJ
AD  - Department of Neurology, the First Affiliated Hospital of Chongqing Medical 
      University, Chongqing Key Laboratory of Neurology, Chongqing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Presenilin-1)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.6.1.- (Peptide Elongation Factor Tu)
SB  - IM
MH  - Alzheimer Disease/genetics/metabolism/*pathology
MH  - Amyloid Precursor Protein Secretases/genetics/*metabolism
MH  - Amyloid beta-Protein Precursor/physiology
MH  - Animals
MH  - *Disease Models, Animal
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitochondria/metabolism/*pathology
MH  - Peptide Elongation Factor Tu/genetics/*metabolism
MH  - Phosphorylation
MH  - Presenilin-1/physiology
MH  - Reactive Oxygen Species/*metabolism
OTO - NOTNLM
OT  - BACE1 translation
OT  - RNA stability
OT  - ROS
OT  - TUFM
OT  - Tau
OT  - apoptosis
OT  - beta-amyloid protein
EDAT- 2021/03/29 06:00
MHDA- 2021/07/20 06:00
CRDT- 2021/03/28 21:13
PHST- 2021/01/20 00:00 [revised]
PHST- 2020/11/06 00:00 [received]
PHST- 2021/02/01 00:00 [accepted]
PHST- 2021/03/28 21:13 [entrez]
PHST- 2021/03/29 06:00 [pubmed]
PHST- 2021/07/20 06:00 [medline]
AID - 10.1096/fj.202002461R [doi]
PST - ppublish
SO  - FASEB J. 2021 May;35(5):e21445. doi: 10.1096/fj.202002461R.