PMID- 27371338
OWN - NLM
STAT- MEDLINE
DCOM- 20170328
LR  - 20171116
IS  - 1472-8206 (Electronic)
IS  - 0767-3981 (Linking)
VI  - 30
IP  - 6
DP  - 2016 Dec
TI  - Protective effects of PF-4708671 against N-methyl-d-aspartic acid-induced retinal 
      damage in rats.
PG  - 529-536
LID - 10.1111/fcp.12216 [doi]
AB  - We previously demonstrated that rapamycin, an inhibitor of the mammalian target 
      of rapamycin (mTOR), protects against N-methyl-d-aspartic acid (NMDA)-induced 
      retinal damage in rats. Rapamycin inhibits mTOR activity, thereby preventing the 
      phosphorylation of ribosomal protein S6, which is a downstream target of S6 
      kinase. Therefore, we aimed to determine whether PF-4708671, an inhibitor of S6 
      kinase, protects against NMDA-induced retinal injury. Intravitreal injection of 
      NMDA (200 nmol/eye) caused cell loss in the ganglion cell layer and 
      neuroinflammatory responses, such as an increase in the number of CD45-positive 
      leukocytes and Iba1-positive microglia. Surprisingly, simultaneous injection of 
      PF-4708671 (50 nmol/eye) with NMDA significantly attenuated these responses 
      without affecting phosphorylated S6 levels. These results suggest that PF-4708671 
      and rapamycin likely protect against NMDA-induced retinal damage via distinct 
      pathways. The neuroprotective effect of PF-4708671 is unlikely to be associated 
      with inhibition of the S6 kinase, even though PF-4708671 is reported to be a S6 
      kinase inhibitor.
CI  - (c) 2016 Societe Francaise de Pharmacologie et de Therapeutique.
FAU - Hayashi, Ikumi
AU  - Hayashi I
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
FAU - Aoki, Yuto
AU  - Aoki Y
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
FAU - Ushikubo, Hiroko
AU  - Ushikubo H
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
FAU - Asano, Daiki
AU  - Asano D
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
FAU - Mori, Asami
AU  - Mori A
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
FAU - Sakamoto, Kenji
AU  - Sakamoto K
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
FAU - Nakahara, Tsutomu
AU  - Nakahara T
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
FAU - Ishii, Kunio
AU  - Ishii K
AD  - Department of Molecular Pharmacology, Kitasato University School of 
      Pharmaceutical Sciences, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
LA  - eng
PT  - Journal Article
DEP - 20160810
PL  - England
TA  - Fundam Clin Pharmacol
JT  - Fundamental & clinical pharmacology
JID - 8710411
RN  - 0 (Aif1 protein, rat)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Imidazoles)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (PF-4708671)
RN  - 0 (Piperazines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Calcium-Binding Proteins/metabolism
MH  - Imidazoles/*pharmacology
MH  - Kidney Diseases/*chemically induced/*drug therapy/metabolism
MH  - Leukocyte Common Antigens/metabolism
MH  - Leukocytes/drug effects/metabolism
MH  - Male
MH  - Microfilament Proteins/metabolism
MH  - Microglia/drug effects/metabolism
MH  - N-Methylaspartate/*pharmacology
MH  - Neuroprotective Agents/*pharmacology
MH  - Phosphorylation/drug effects
MH  - Piperazines/*pharmacology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Sirolimus/pharmacology
OTO - NOTNLM
OT  - S6 kinase
OT  - excitotoxicity
OT  - mammalian target of rapamycin
OT  - neuroinflammation
EDAT- 2016/07/03 06:00
MHDA- 2017/03/30 06:00
CRDT- 2016/07/03 06:00
PHST- 2015/09/01 00:00 [received]
PHST- 2016/05/13 00:00 [revised]
PHST- 2016/06/29 00:00 [accepted]
PHST- 2016/07/03 06:00 [pubmed]
PHST- 2017/03/30 06:00 [medline]
PHST- 2016/07/03 06:00 [entrez]
AID - 10.1111/fcp.12216 [doi]
PST - ppublish
SO  - Fundam Clin Pharmacol. 2016 Dec;30(6):529-536. doi: 10.1111/fcp.12216. Epub 2016 
      Aug 10.