PMID- 26277554
OWN - NLM
STAT- MEDLINE
DCOM- 20160617
LR  - 20150921
IS  - 1879-0542 (Electronic)
IS  - 0165-2478 (Linking)
VI  - 167
IP  - 2
DP  - 2015 Oct
TI  - Extracellular ATP induces unconventional release of glyceraldehyde-3-phosphate 
      dehydrogenase from microglial cells.
PG  - 116-24
LID - S0165-2478(15)30016-X [pii]
LID - 10.1016/j.imlet.2015.08.002 [doi]
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme that 
      is predominantly localized in the cytoplasm. However, recent studies have 
      suggested that GAPDH is released by various cells and that extracellular GAPDH is 
      involved in the regulation of neuritogenesis in neuronal cells. It has also been 
      reported that GAPDH is expressed on the surfaces of macrophages and functions as 
      a transferrin receptor. However, since GAPDH is a leaderless protein the 
      mechanisms by which it reaches the extracellular environment remain unclear. 
      Here, we examined the role of P2X7 receptor (P2X7R), an ATP-gated cation channel, 
      in the unconventional release of GAPDH from microglial cells, the resident 
      macrophages in the brain. The activation of P2X7R by ATP triggered GAPDH release 
      from lipopolysaccharide (LPS)-primed microglial cells. ATP-induced microvesicle 
      formation, exosome release, and K(+) efflux followed by caspase-1 activation are 
      likely involved in the GAPDH release, but ATP-induced dilatation of membrane 
      pores and lysosome exocytosis are not. It was also demonstrated that exogenous 
      GAPDH facilitated LPS-induced phosphorylation of p38 MAP kinase in microglial 
      cells. These findings suggest that P2X7R plays an important role in the 
      unconventional release of GAPDH from microglial cells, and the GAPDH released 
      into the extracellular space might be involved in the regulation of the 
      neuroinflammatory response in the brain.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Takenouchi, Takato
AU  - Takenouchi T
AD  - Animal Immune and Cell Biology Research Unit, Division of Animal Sciences, 
      National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki 
      305-8634, Japan. Electronic address: ttakenou@affrc.go.jp.
FAU - Tsukimoto, Mitsutoshi
AU  - Tsukimoto M
AD  - Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, 
      Noda, Chiba 278-8510, Japan.
FAU - Iwamaru, Yoshifumi
AU  - Iwamaru Y
AD  - Prion Disease Research Center, National Institute of Animal Health, 3-1-5 
      Kannondai, Tsukuba, Ibaraki 305-8602, Japan.
FAU - Sugama, Shuei
AU  - Sugama S
AD  - Department of Physiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 
      113-8602, Japan.
FAU - Sekiyama, Kazunari
AU  - Sekiyama K
AD  - Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical 
      Science, Tokyo 156-0057, Japan.
FAU - Sato, Mitsuru
AU  - Sato M
AD  - Animal Immune and Cell Biology Research Unit, Division of Animal Sciences, 
      National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki 
      305-8634, Japan.
FAU - Kojima, Shuji
AU  - Kojima S
AD  - Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, 
      Noda, Chiba 278-8510, Japan.
FAU - Hashimoto, Makoto
AU  - Hashimoto M
AD  - Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical 
      Science, Tokyo 156-0057, Japan.
FAU - Kitani, Hiroshi
AU  - Kitani H
AD  - Animal Immune and Cell Biology Research Unit, Division of Animal Sciences, 
      National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki 
      305-8634, Japan. Electronic address: kitani@affrc.go.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150812
PL  - Netherlands
TA  - Immunol Lett
JT  - Immunology letters
JID - 7910006
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Purinergic P2X7)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Adenosine Triphosphate/*metabolism
MH  - Caspase 1/metabolism
MH  - Cells, Cultured
MH  - Enzyme Activation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Exocytosis/immunology
MH  - Extracellular Space
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Lipopolysaccharides/immunology
MH  - Lysosomes/immunology/metabolism
MH  - Microglia/*immunology/*metabolism
MH  - Phosphorylation
MH  - Potassium/metabolism
MH  - Primary Cell Culture
MH  - Receptors, Purinergic P2X7/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - Glyceraldehyde-3-phosphate dehydrogenase
OT  - Microglial cells
OT  - P2X7 receptor
OT  - Unconventional release
EDAT- 2015/08/19 06:00
MHDA- 2016/06/18 06:00
CRDT- 2015/08/17 06:00
PHST- 2015/05/20 00:00 [received]
PHST- 2015/07/16 00:00 [revised]
PHST- 2015/08/10 00:00 [accepted]
PHST- 2015/08/17 06:00 [entrez]
PHST- 2015/08/19 06:00 [pubmed]
PHST- 2016/06/18 06:00 [medline]
AID - S0165-2478(15)30016-X [pii]
AID - 10.1016/j.imlet.2015.08.002 [doi]
PST - ppublish
SO  - Immunol Lett. 2015 Oct;167(2):116-24. doi: 10.1016/j.imlet.2015.08.002. Epub 2015 
      Aug 12.