PMID- 27847386
OWN - NLM
STAT- MEDLINE
DCOM- 20170411
LR  - 20210927
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 22
DP  - 2016 Nov 12
TI  - 17beta-Estradiol Inhibites Tumor Necrosis Factor-alpha Induced Apoptosis of Human 
      Nucleus Pulposus Cells via the PI3K/Akt Pathway.
PG  - 4312-4322
AB  - BACKGROUND Tumor necrosis factor-alpha (TNF-alpha) has been widely known to induce 
      degeneration of nucleus pulposus cells (NPCs). 17beta-estradiol (17beta-E2) has been 
      broadly proven for its function of suppressing cell apoptosis. The aim of this 
      study is to explore whether 17beta-E2 protects apoptosis of human NPCs induced by 
      TNF-alpha via the PI3K/AKT pathway. MATERIAL AND METHODS NPCs were divided into four 
      groups: control, TNF-alpha (100 ng/mL), TNF-alpha (100 ng/mL) with pretreated 17beta-E2 (10 
      um/L), TNF-alpha (100 ng/mL) with pretreated 17beta-E2 (10 um/L) and MK2206 (10 um/L, 
      inhibitor of the PI3K/AKT pathway). Flow cytometry was used to measure the 
      apoptotic incidence. Inverted phase-contrast microscopy was used to accomplish 
      the morphological observation for apoptosis of treated cells. Additionally, Cell 
      Counting Kit 8 (CCK-8) assay was used to detected cell proliferation. Western 
      blot and quantitative real-time PCR (qRT-PCR) were applied to explore the 
      expression of pro-caspase-3, caspase-3/p17, cleaved PARP, PARP, Akt, and 
      phospho-Akt (p-Akt). RESULTS First, inverted phase-contrast microscopy, CCK-8, 
      and flow cytometry showed that TNF-alpha induced marked apoptosis, which was 
      abolished by 17beta-E2. Furthermore, Western blot and qRT-PCR showed that 17beta-E2 
      protects TNF-alpha which can induced apoptosis by upregulating p-Akt, whereas Akt was 
      essentially constant. Our data revealed that p-Akt expression peaked at 24 hours 
      in a time-dependent manner (0-48 hours) after treating with TNF-alpha; and the p-Akt 
      expression generally increased in a time-dependent manner (0-48 hours) after 
      treating with TNF-alpha and 17beta-E2. CONCLUSIONS 17beta-E2 is shown to protect NPCs 
      against TNF-alpha induced apoptosis by upregulating p-Akt in the PI3K/AKT pathway. 
      17beta-E2 generally increases expression of p-Akt.
FAU - Wang, Tao
AU  - Wang T
AD  - Department of Spinal Surgery, The Third Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China (mainland).
FAU - Yang, Si-Dong
AU  - Yang SD
AD  - Department of Spinal Surgery, The Third Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China (mainland).
FAU - Liu, Sen
AU  - Liu S
AD  - Department of Spinal Surgery, The Third Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China (mainland).
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Spinal Surgery, The Third Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China (mainland).
FAU - Liu, Huan
AU  - Liu H
AD  - Department of Spinal Surgery, The Third Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China (mainland).
FAU - Ding, Wen Yuan
AU  - Ding WY
AD  - Department of Spinal Surgery, The Third Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20161112
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Protective Agents)
RN  - 0 (TNF protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
EIN - Med Sci Monit. 2021 Aug 06;27:e934008. PMID: 34355701
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Estradiol/*pharmacology
MH  - Humans
MH  - Nucleus Pulposus/*cytology/*drug effects/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation
MH  - Protective Agents/pharmacology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
MH  - Up-Regulation/drug effects
PMC - PMC5115218
OTO - NOTNLM
OT  - Accessory nerve
OT  - Estriol
OT  - Tumor Necrosis Factors
EDAT- 2016/11/17 06:00
MHDA- 2017/04/12 06:00
PMCR- 2016/11/12
CRDT- 2016/11/17 06:00
PHST- 2016/11/17 06:00 [entrez]
PHST- 2016/11/17 06:00 [pubmed]
PHST- 2017/04/12 06:00 [medline]
PHST- 2016/11/12 00:00 [pmc-release]
AID - 900310 [pii]
AID - 10.12659/MSM.900310 [doi]
PST - epublish
SO  - Med Sci Monit. 2016 Nov 12;22:4312-4322. doi: 10.12659/MSM.900310.