PMID- 29149631
OWN - NLM
STAT- MEDLINE
DCOM- 20180926
LR  - 20210109
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Print)
IS  - 0197-4580 (Linking)
VI  - 62
DP  - 2018 Feb
TI  - Prostaglandin J2 promotes O-GlcNAcylation raising APP processing by alpha- and 
      beta-secretases: relevance to Alzheimer's disease.
PG  - 130-145
LID - S0197-4580(17)30348-2 [pii]
LID - 10.1016/j.neurobiolaging.2017.10.009 [doi]
AB  - Regulation of the amyloid precursor protein (APP) processing by alpha- and 
      beta-secretases is of special interest to Alzheimer's disease (AD), as these 
      proteases prevent or mediate amyloid beta formation, respectively. 
      Neuroinflammation is also implicated in AD. Our data demonstrate that the 
      endogenous mediator of inflammation prostaglandin J2 (PGJ2) promotes full-length 
      APP (FL-APP) processing by alpha- and beta-secretases. The decrease in FL-APP was 
      independent of proteasomal, lysosomal, calpain, caspase, and gamma-secretase 
      activities. Moreover, PGJ2-treatment promoted cleavage of secreted APP, 
      specifically sAPPalpha and sAPPbeta, generated by alpha and beta-secretase, respectively. 
      Notably, PGJ2-treatment induced caspase-dependent cleavage of sAPPbeta. 
      Mechanistically, PGJ2-treatment selectively diminished mature (O- and 
      N-glycosylated) but not immature (N-glycosylated only) FL-APP. PGJ2-treatment 
      also increased the overall levels of protein O-GlcNAcylation, which occurs within 
      the nucleocytoplasmic compartment. It is known that APP undergoes O-GlcNAcylation 
      and that the latter protects proteins from proteasomal degradation. Our results 
      suggest that by increasing protein O-GlcNAcylation levels, PGJ2 renders mature 
      APP less prone to proteasomal degradation, thus shunting APP toward processing by 
      alpha- and beta-secretases.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Jean-Louis, Teneka
AU  - Jean-Louis T
AD  - Department of Biological Sciences, Hunter College, Biology and Biochemistry 
      Programs, Graduate Center, The City University of New York, New York, NY, USA.
FAU - Rockwell, Patricia
AU  - Rockwell P
AD  - Department of Biological Sciences, Hunter College, Biology and Biochemistry 
      Programs, Graduate Center, The City University of New York, New York, NY, USA.
FAU - Figueiredo-Pereira, Maria E
AU  - Figueiredo-Pereira ME
AD  - Department of Biological Sciences, Hunter College, Biology and Biochemistry 
      Programs, Graduate Center, The City University of New York, New York, NY, USA. 
      Electronic address: pereira@genectr.hunter.cuny.edu.
LA  - eng
GR  - G12 MD007599/MD/NIMHD NIH HHS/United States
GR  - R25 GM060665/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20171114
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 60203-57-8 (9-deoxy-delta-9-prostaglandin D2)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - RXY07S6CZ2 (Prostaglandin D2)
SB  - IM
MH  - Alzheimer Disease/*etiology/*metabolism
MH  - Amyloid Precursor Protein Secretases/*physiology
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Caspases/physiology
MH  - Cells, Cultured
MH  - Cytoplasm/metabolism
MH  - Female
MH  - Glycosylation
MH  - Humans
MH  - Inflammation/etiology/metabolism
MH  - Male
MH  - Prostaglandin D2/*analogs & derivatives/physiology
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Proteolysis
MH  - Rats, Sprague-Dawley
MH  - Tumor Cells, Cultured
PMC - PMC5743611
MID - NIHMS915858
OTO - NOTNLM
OT  - APP
OT  - Apoptosis
OT  - O-GlcNAcylation
OT  - Prostaglandin J2
OT  - Secretases
COIS- Disclosure Statement: The authors declare no conflicts of interest.
EDAT- 2017/11/18 06:00
MHDA- 2018/09/27 06:00
PMCR- 2019/02/01
CRDT- 2017/11/18 06:00
PHST- 2017/08/07 00:00 [received]
PHST- 2017/09/26 00:00 [revised]
PHST- 2017/10/11 00:00 [accepted]
PHST- 2017/11/18 06:00 [pubmed]
PHST- 2018/09/27 06:00 [medline]
PHST- 2017/11/18 06:00 [entrez]
PHST- 2019/02/01 00:00 [pmc-release]
AID - S0197-4580(17)30348-2 [pii]
AID - 10.1016/j.neurobiolaging.2017.10.009 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2018 Feb;62:130-145. doi: 10.1016/j.neurobiolaging.2017.10.009. 
      Epub 2017 Nov 14.