PMID- 27635402
OWN - NLM
STAT- MEDLINE
DCOM- 20170609
LR  - 20200914
IS  - 2314-6753 (Electronic)
IS  - 2314-6745 (Print)
VI  - 2016
DP  - 2016
TI  - High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix 
      Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus 
      Cells.
PG  - 3765173
LID - 10.1155/2016/3765173 [doi]
LID - 3765173
AB  - Objectives. To investigate whether high glucose-induced oxidative stress is 
      implicated in apoptosis of rat nucleus pulposus cells (NPCs) and abnormal 
      expression of critical genes involved in the metabolic balance of extracellular 
      matrix (ECM). Methods. NPCs were cultured with various concentrations of glucose 
      to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM) 
      were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 
      202190. Reactive oxygen species (ROS) production was evaluated. Activation of p38 
      MAPK was measured by Western blot. The expression of ECM metabolism-related 
      genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 
      9 (Sox-9), matrix metalloproteinase 3 (MMP-3), and tissue inhibitor of 
      metalloproteinase 1 (TIMP-1), was analyzed by semiquantitative RT-PCR. Results. 
      High glucose reduced viability of NPCs and induced apoptosis. High glucose 
      resulted in increased ROS generation and p38 MAPK activation. In addition, it 
      negatively regulated the expression of type II collagen, aggrecan, Sox-9, and 
      TIMP-1 and positively regulated MMP-3 expression. These results were changed by 
      pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might 
      promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its 
      anabolic activities, possibly through a p38 MAPK-dependent oxidative stress 
      mechanism.
FAU - Cheng, Xiaofei
AU  - Cheng X
AD  - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic 
      Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of 
      Medicine, 639 Zhizaoju Road, Shanghai 200011, China.
FAU - Ni, Bin
AU  - Ni B
AD  - Department of Orthopedics, Changzheng Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Zhang, Feng
AU  - Zhang F
AD  - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic 
      Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of 
      Medicine, 639 Zhizaoju Road, Shanghai 200011, China.
FAU - Hu, Ying
AU  - Hu Y
AD  - Department of Toxicity Evaluation, Shanghai Municipal Center for Disease Control 
      and Prevention, Shanghai, China.
FAU - Zhao, Jie
AU  - Zhao J
AUID- ORCID: 0000-0002-4504-8193
AD  - Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic 
      Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of 
      Medicine, 639 Zhizaoju Road, Shanghai 200011, China.
LA  - eng
PT  - Journal Article
DEP - 20160822
PL  - England
TA  - J Diabetes Res
JT  - Journal of diabetes research
JID - 101605237
RN  - 0 (Aggrecans)
RN  - 0 (Collagen Type II)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (SOX9 Transcription Factor)
RN  - 0 (TIMP1 protein, rat)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - IY9XDZ35W2 (Glucose)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Aggrecans/drug effects/genetics
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Blotting, Western
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Collagen Type II/drug effects/genetics
MH  - Extracellular Matrix/*drug effects/metabolism
MH  - Free Radical Scavengers/pharmacology
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Hyperglycemia/genetics/metabolism
MH  - Matrix Metalloproteinase 3/drug effects/genetics
MH  - Nucleus Pulposus/cytology/*drug effects/metabolism
MH  - Oxidative Stress/*drug effects
MH  - RNA, Messenger/*drug effects/metabolism
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - SOX9 Transcription Factor/drug effects/genetics
MH  - Tissue Inhibitor of Metalloproteinase-1/drug effects/genetics
MH  - p38 Mitogen-Activated Protein Kinases/*drug effects/metabolism
PMC - PMC5011214
EDAT- 2016/09/17 06:00
MHDA- 2017/06/10 06:00
PMCR- 2016/08/22
CRDT- 2016/09/17 06:00
PHST- 2015/11/16 00:00 [received]
PHST- 2015/12/25 00:00 [revised]
PHST- 2015/12/28 00:00 [accepted]
PHST- 2016/09/17 06:00 [entrez]
PHST- 2016/09/17 06:00 [pubmed]
PHST- 2017/06/10 06:00 [medline]
PHST- 2016/08/22 00:00 [pmc-release]
AID - 10.1155/2016/3765173 [doi]
PST - ppublish
SO  - J Diabetes Res. 2016;2016:3765173. doi: 10.1155/2016/3765173. Epub 2016 Aug 22.