PMID- 29445584
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2164-7844 (Print)
IS  - 2164-7860 (Electronic)
IS  - 2164-7844 (Linking)
VI  - 7
IP  - 1
DP  - 2018
TI  - Acid-Sensing Ion Channel 1a Regulates Fate of Rat Nucleus Pulposus Cells in Acid 
      Stimulus Through Endoplasmic Reticulum Stress.
PG  - 2-9
LID - 10.1089/biores.2017.0049 [doi]
AB  - Acid-sensing ion channel 1a (ASIC1a) participates in human intervertebral disc 
      degeneration (IVDD) and regulates the destiny of nucleus pulposus cells (NPCs) in 
      acid stimulus. However, the mechanism of ASIC1a activation and its downstream 
      pathway remain unclear. Endoplasmic reticulum (ER) stress also participates in 
      the acid-induced apoptosis of NPCs. The main purpose of this study was to 
      investigate whether there is any connection between ASIC1a and ER stress in an 
      acid-induced nucleus pulposus degeneration model. The IVDs of Sprague-Dawley rats 
      were stained by immunohistochemical staining to evaluate the expression of ASIC1a 
      in normal and degenerated rat nucleus pulposus. ASIC1a expression was also 
      quantified by quantitative real-time-polymerase chain reaction and Western 
      blotting analysis. NPCs were exposed to the culture media with acidity at pH 7.2 
      and 6.5 for 24 h, with or without 4-phenylbutyrate (4-PBA, a blocker of the ER 
      stress pathway). Cell apoptosis was examined by Annexin V/Propidium Iodide (PI) 
      staining and was quantified using flow cytometry analysis. ASIC1a-mediated 
      intracellular calcium was determined by Ca(2+) imaging using Fura-2-AM. 
      Acidity-induced changes in ER stress markers were studied using Western blotting 
      analysis. In vivo, ASIC1a expression was upregulated in natural degeneration. In 
      vitro, acid stimulus increased intracellular calcium levels, but this effect was 
      blocked by knockdown of ASIC1a, and this reversal was partly inhibited by 4-PBA. 
      In addition, blockade of ASIC1a reduced expression of ER stress markers, 
      especially the proapoptotic markers. ASIC1a partly regulates ER stress and 
      promotes apoptosis of NPCs under acid stimulus and may be a novel therapeutic 
      target in IVDD.
FAU - Xie, Zhi-Yang
AU  - Xie ZY
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Chen, Lu
AU  - Chen L
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Zhang, Cong
AU  - Zhang C
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Liu, Lei
AU  - Liu L
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Wang, Feng
AU  - Wang F
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Cai, Feng
AU  - Cai F
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
AD  - Department of Orthopedics, First Affiliated Hospital of Soochow University, 
      Suzhou, China.
FAU - Wang, Xiao-Hu
AU  - Wang XH
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Shi, Rui
AU  - Shi R
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Sinkemani, Arjun
AU  - Sinkemani A
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Yu, Hao-Min
AU  - Yu HM
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Hong, Xin
AU  - Hong X
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Wu, Xiao-Tao
AU  - Wu XT
AD  - Department of Spine Surgery, ZhongDa Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20180201
PL  - United States
TA  - Biores Open Access
JT  - BioResearch open access
JID - 101579333
PMC - PMC5808393
OTO - NOTNLM
OT  - acid-sensing ion channel 1a
OT  - apoptosis
OT  - endoplasmic reticulum stress
OT  - intervertebral disc degeneration
OT  - nucleus pulposus
COIS- No competing financial interests exist.
EDAT- 2018/02/16 06:00
MHDA- 2018/02/16 06:01
PMCR- 2018/02/01
CRDT- 2018/02/16 06:00
PHST- 2018/02/16 06:00 [entrez]
PHST- 2018/02/16 06:00 [pubmed]
PHST- 2018/02/16 06:01 [medline]
PHST- 2018/02/01 00:00 [pmc-release]
AID - 10.1089/biores.2017.0049 [pii]
AID - 10.1089/biores.2017.0049 [doi]
PST - epublish
SO  - Biores Open Access. 2018 Feb 1;7(1):2-9. doi: 10.1089/biores.2017.0049. 
      eCollection 2018.