PMID- 26648565
OWN - NLM
STAT- MEDLINE
DCOM- 20161031
LR  - 20211203
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 13
IP  - 2
DP  - 2016 Feb
TI  - Knockdown of NogoA prevents MPP+‑induced neurotoxicity in PC12 cells via the 
      mTOR/STAT3 signaling pathway.
PG  - 1427-33
LID - 10.3892/mmr.2015.4637 [doi]
AB  - NogoA is a myelin‑associated protein, which is important in the inhibition of 
      axonal fiber growth and in regeneration following injury of the mammalian central 
      nervous system. A previous study suggested that NogoA may be key in the process 
      of Parkinson's disease (PD), which is the second most common chronic 
      neurodegenerative disorder worldwide. The regulatory mechanism underlying the 
      effect of NogoA on the process of PD remains to be fully elucidated. The present 
      study aimed to investigate the effect and underlying mechanism of NogoA on 
      cellular viability, apoptosis and autophagy induced by 
      1-methyl-4-phenylpyridinium (MPP+) in PC12 cells, a commonly used in vitro PD 
      model. PC12 cells were treated with 1 mM MPP+ for 24 h and the cells were 
      harvested for western blotting. The results demonstrated that the protien 
      expression levels of NogoA were increased in the PC12 cells treated with MPP+. 
      Subsequently, NogoA small interfering RNA was synthesized and transfected into 
      PC12 cells to silence the expression of NogoA. NogoA knockdown significantly 
      reduced the MPP+‑induced decrease in cell viability and apoptosis, detected using 
      a cell counting kit‑8 and flow cytometric analysis, respectively. Interference in 
      the expression of NogoA increased the MPP+‑induced decrease in mitochondrial 
      membrane potential, determined quantitatively by flow cytometry using JC-1 dye, 
      and the protein levels of Beclin‑1. In addition, MPP+ treatment activated the 
      mammalian target of rapamycin (mTOR)/signal transducer and activator of 
      transcription 3 (STAT3) signaling pathway. Knockdown of NogoA significantly 
      inhibited the expression levels of mTOR and STAT3. Furthermore, overexpression of 
      NogoA had similar neurotoxic effects on the PC12 cells as MPP+ treatment. 
      Treatment with rapamycin, an inhibitor of the mTOR/STAT3 signaling pathway had a 
      similar effect to that of NogoA knockdown in the MPP+‑treated PC12 cells. Taken 
      together, the results from the present study demonstrated that NogoA may regulate 
      MPP+‑induced neurotoxicity in PC12 cells via the mTOR/STAT3 signaling pathway and 
      provided an explanation regarding the regulatory mechanism of NogoA on the 
      process of PD.
FAU - Zhong, Jianbin
AU  - Zhong J
AD  - Department of Neurology, Zeng Cheng People's Hospital and Boji Hospital of Sun 
      Yat‑sen University, Guangzhou, Guangdong 511300, P.R. China.
FAU - Li, Xie
AU  - Li X
AD  - Department of Neurology, Zeng Cheng People's Hospital and Boji Hospital of Sun 
      Yat‑sen University, Guangzhou, Guangdong 511300, P.R. China.
FAU - Wan, Limei
AU  - Wan L
AD  - Department of Neurology, Zeng Cheng People's Hospital and Boji Hospital of Sun 
      Yat‑sen University, Guangzhou, Guangdong 511300, P.R. China.
FAU - Chen, Zhibang
AU  - Chen Z
AD  - Department of Neurology, Zeng Cheng People's Hospital and Boji Hospital of Sun 
      Yat‑sen University, Guangzhou, Guangdong 511300, P.R. China.
FAU - Zhong, Simin
AU  - Zhong S
AD  - Department of Neurology, Zeng Cheng People's Hospital and Boji Hospital of Sun 
      Yat‑sen University, Guangzhou, Guangdong 511300, P.R. China.
FAU - Xiao, Songhua
AU  - Xiao S
AD  - Department of Neurology, Sun Yat‑sen Memorial Hospital of Sun Yat‑sen University, 
      Guangzhou, Guangdong 511300, P.R. China.
FAU - Yan, Zhengwen
AU  - Yan Z
AD  - Department of Neurology, Sun Yat‑sen Memorial Hospital of Sun Yat‑sen University, 
      Guangzhou, Guangdong 511300, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151204
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Beclin-1)
RN  - 0 (Becn1 protein, rat)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Myelin Proteins)
RN  - 0 (Neurotoxins)
RN  - 0 (Nogo Proteins)
RN  - 0 (Nogo Receptor 1)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Rtn4 protein, rat)
RN  - 0 (Rtn4r protein, rat)
RN  - 0 (STAT3 Transcription Factor)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - R865A5OY8J (1-Methyl-4-phenylpyridinium)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - 1-Methyl-4-phenylpyridinium/*toxicity
MH  - Animals
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Autophagy/drug effects
MH  - Beclin-1
MH  - Cell Survival
MH  - GPI-Linked Proteins/metabolism
MH  - *Gene Knockdown Techniques
MH  - Gene Silencing/drug effects
MH  - Myelin Proteins/*metabolism
MH  - Neurotoxins/*toxicity
MH  - Nogo Proteins
MH  - Nogo Receptor 1
MH  - PC12 Cells
MH  - Rats
MH  - Receptors, Cell Surface/metabolism
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2015/12/10 06:00
MHDA- 2016/11/01 06:00
CRDT- 2015/12/10 06:00
PHST- 2015/01/27 00:00 [received]
PHST- 2015/11/17 00:00 [accepted]
PHST- 2015/12/10 06:00 [entrez]
PHST- 2015/12/10 06:00 [pubmed]
PHST- 2016/11/01 06:00 [medline]
AID - 10.3892/mmr.2015.4637 [doi]
PST - ppublish
SO  - Mol Med Rep. 2016 Feb;13(2):1427-33. doi: 10.3892/mmr.2015.4637. Epub 2015 Dec 4.