PMID- 26707978
OWN - NLM
STAT- MEDLINE
DCOM- 20161019
LR  - 20220111
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1632
DP  - 2016 Feb 1
TI  - Stabilization of HIF-1alpha by FG-4592 promotes functional recovery and neural 
      protection in experimental spinal cord injury.
PG  - 19-26
LID - S0006-8993(15)00956-7 [pii]
LID - 10.1016/j.brainres.2015.12.017 [doi]
AB  - Previous studies have shown that inhibition of prolyl hydroxylase(PHD) stabilizes 
      Hypoxia-inducible factor 1, alpha subunit(HIF-1alpha), increases tolerance to 
      hypoxia, and improves the prognosis of many diseases. However, the role of PHD 
      inhibitor (PHDI) in the recovery of spinal cord injury remains controversial. In 
      this study, we investigated the protective role of a novel PHDI FG-4592 both in 
      vivo and in vitro. FG-4592 treatment stabilized HIF1alpha expression both in PC12 
      cells and in spinal cord. FG-4592 treatment significantly inhibited tert-Butyl 
      hydroperoxide(TBHP)-induced apoptosis and increases the survival of neuronal 
      PC-12 cells. FG-4592 administration also improved recovery and increased the 
      survival of neurons in spinal cord lesions in the mice model. Combination therapy 
      including the specific HIF-1alpha blocker YC-1 down-regulated the HIF-1alpha expression 
      and partially abolished the protective effect of FG-4592. Taken together, our 
      results revealed that the role of FG-4592 in SCI recovery is related to the 
      stabilization of HIF-1alpha and inhibition of apoptosis. Overall, our study suggests 
      that PHDIs may be feasible candidates for therapeutic intervention after SCI and 
      central nervous system disorders in humans.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Wu, Kai
AU  - Wu K
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China.
FAU - Zhou, Kailiang
AU  - Zhou K
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China.
FAU - Wang, Yongli
AU  - Wang Y
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China.
FAU - Zhou, Yifei
AU  - Zhou Y
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China.
FAU - Tian, Naifeng
AU  - Tian N
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China.
FAU - Wu, Yaosen
AU  - Wu Y
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China.
FAU - Chen, Deheng
AU  - Chen D
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China.
FAU - Zhang, Di
AU  - Zhang D
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China.
FAU - Wang, Xiangyang
AU  - Wang X
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China.
FAU - Xu, Huazi
AU  - Xu H
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China. Electronic address: 
      spinexu@163.com.
FAU - Zhang, Xiaolei
AU  - Zhang X
AD  - Department of Orthopaedics, The Second affiliated hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang Province, China; Zhejiang Provincial Key laboratory 
      of orthopaedics, Wenzhou, Zhejiang Province, China. Electronic address: 
      callmeroger@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151217
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Isoquinolines)
RN  - 0 (Neuroprotective Agents)
RN  - TE7660XO1C (Glycine)
RN  - X3O30D9YMX (roxadustat)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Glycine/*analogs & derivatives/pharmacology/therapeutic use
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors/*metabolism
MH  - Isoquinolines/pharmacology/*therapeutic use
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - PC12 Cells
MH  - Rats
MH  - Recovery of Function/drug effects/*physiology
MH  - Spinal Cord Injuries/*drug therapy/*metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - HIF1alpha
OT  - Prolyl hydroxylase inhibitor
OT  - Spinal cord injury
EDAT- 2015/12/29 06:00
MHDA- 2016/11/12 06:00
CRDT- 2015/12/29 06:00
PHST- 2015/08/14 00:00 [received]
PHST- 2015/12/04 00:00 [revised]
PHST- 2015/12/11 00:00 [accepted]
PHST- 2015/12/29 06:00 [entrez]
PHST- 2015/12/29 06:00 [pubmed]
PHST- 2016/11/12 06:00 [medline]
AID - S0006-8993(15)00956-7 [pii]
AID - 10.1016/j.brainres.2015.12.017 [doi]
PST - ppublish
SO  - Brain Res. 2016 Feb 1;1632:19-26. doi: 10.1016/j.brainres.2015.12.017. Epub 2015 
      Dec 17.