PMID- 29649627
OWN - NLM
STAT- MEDLINE
DCOM- 20181015
LR  - 20211204
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 103
DP  - 2018 Jul
TI  - Overexpression of HIPK2 attenuates spinal cord injury in rats by modulating 
      apoptosis, oxidative stress, and inflammation.
PG  - 127-134
LID - S0753-3322(17)36963-9 [pii]
LID - 10.1016/j.biopha.2018.03.117 [doi]
AB  - HIPK2 is considered to be a tumor suppressor. It also has been implicated in 
      several functions such as apoptosis and inflammation that are linked to spinal 
      cord injury (SCI). However, whether HIPK2 ameliorates the neurological pain of 
      SCI remains unclear. Here, we investigated the effects of HIPK2 on neurological 
      function, oxidative stress, levels of inflammatory cytokines and expression of 
      Bcl-2/Bax in an SCI model. Firstly, we evaluated the therapeutic effects of HIPK2 
      on neurological pain in the SCI rat using the Basso, Beattie and Bresnahan scores 
      and H & E staining. Overexpression of HIPK2 significantly elevated the levels of 
      brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic 
      factor (GDNF), and reduced the mRNA expression of Nogo-A and RhoA in SCI rats. 
      Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL) assays showed that overexpression of HIPK2 significantly reduced 
      the number of apoptotic cells. Overexpression of HIPK2 also decreased expression 
      of Bax and Caspase-3 and elevated expression of Bcl-2 in the SCI model, 
      indicating that HIPK2 exhibited its protective activity by inhibiting SCI-induced 
      apoptosis. Then, we measured the serum concentrations of malondialdehyde (MDA), 
      superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). 
      We also determined the mRNA and protein levels of nuclear factor-kappaB p65 unit, 
      tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-1beta. HIPK2 overexpression 
      reduced oxidative stress and the levels of inflammatory cytokines compared with 
      SCI control animals. Additionally, acetylation of HIPK2 was reduced in SCI rats. 
      Overexpression of HIPK2 could enhance autophagy by elevating the expression of 
      Beclin-1 and LC3-II while autophagy is regarded as a beneficial regulator to 
      improve spinal cord injury. Together, overexpression of HIPK2 improved contusive 
      SCI induced pain by modulating oxidative stress, Bcl‑2 and Bax signaling, and 
      inflammation, and also regulating autophagy.
CI  - Copyright (c) 2018. Published by Elsevier Masson SAS.
FAU - Li, Renbo
AU  - Li R
AD  - Department of Orthopedics, The First Hospical of China Medical University, 
      Shenyang, Liaoning Province, 110001, China; Third People's Hospital of Dalian, 
      Dalian, Liaoning Province, 116091, China.
FAU - Shang, Jingbo
AU  - Shang J
AD  - Third People's Hospital of Dalian, Dalian, Liaoning Province, 116091, China.
FAU - Zhou, Wei
AU  - Zhou W
AD  - Third People's Hospital of Dalian, Dalian, Liaoning Province, 116091, China.
FAU - Jiang, Li
AU  - Jiang L
AD  - Third People's Hospital of Dalian, Dalian, Liaoning Province, 116091, China.
FAU - Xie, Donghui
AU  - Xie D
AD  - Third People's Hospital of Dalian, Dalian, Liaoning Province, 116091, China.
FAU - Tu, Guanjun
AU  - Tu G
AD  - Department of Orthopedics, The First Hospical of China Medical University, 
      Shenyang, Liaoning Province, 110001, China. Electronic address: tu188@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20180424
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nogo Proteins)
RN  - EC 2.7.11.1 (HIPK2 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/metabolism
MH  - Antioxidants/metabolism
MH  - *Apoptosis
MH  - Behavior, Animal
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Count
MH  - Glial Cell Line-Derived Neurotrophic Factor/metabolism
MH  - Inflammation/*pathology
MH  - Male
MH  - Nogo Proteins/metabolism
MH  - *Oxidative Stress
MH  - PC12 Cells
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord/metabolism/pathology
MH  - Spinal Cord Injuries/*enzymology/*pathology
MH  - rhoA GTP-Binding Protein/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Homeodomain-interacting protein kinase 2 (HIPK2)
OT  - Inflammation
OT  - Nuclear factor-kappaB
OT  - Oxidative stress
OT  - Spinal cord injury
EDAT- 2018/04/13 06:00
MHDA- 2018/10/16 06:00
CRDT- 2018/04/13 06:00
PHST- 2017/12/19 00:00 [received]
PHST- 2018/03/20 00:00 [revised]
PHST- 2018/03/20 00:00 [accepted]
PHST- 2018/04/13 06:00 [pubmed]
PHST- 2018/10/16 06:00 [medline]
PHST- 2018/04/13 06:00 [entrez]
AID - S0753-3322(17)36963-9 [pii]
AID - 10.1016/j.biopha.2018.03.117 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2018 Jul;103:127-134. doi: 10.1016/j.biopha.2018.03.117. 
      Epub 2018 Apr 24.