PMID- 21068071
OWN - NLM
STAT- MEDLINE
DCOM- 20110217
LR  - 20211020
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 208
IP  - 2
DP  - 2011 Feb
TI  - Estrogen receptor agonists and estrogen attenuate TNF-alpha-induced apoptosis in 
      VSC4.1 motoneurons.
PG  - 171-82
LID - 10.1677/JOE-10-0338 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) may cause apoptosis and inflammation in 
      amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI). Recent studies 
      suggest that estrogen (EST) provides neuroprotection against SCI. We tested 
      whether 1,3,5-tris (4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) (EST receptor 
      alpha (ERalpha) agonist), 2,3-bis (4-hydroxyphenyl) propionitrile (DPN) (EST receptor 
      beta (ERbeta) agonist), or EST itself would prevent apoptosis in VSC4.1 motoneurons 
      following exposure to TNF-alpha. Cells were exposed to TNF-alpha and 15 min later treated 
      with PPT, DPN, or EST. Posttreatment with 50 nM PPT, 50 nM DPN, or 150 nM EST 
      prevented cell death in VSC4.1 motoneurons. Treatment of VSC4.1 motoneurons with 
      PPT, DPN, or EST induced overexpression of ERalpha, ERbeta, or both, which contributed 
      to neuroprotection by upregulating expression of anti-apoptotic proteins (p-AKT, 
      p-CREB, Bcl-2, and p-Src). Our analyses also revealed that EST agonists and EST 
      increased phosphorylation of extracellular signal-regulated kinase (ERK). The 
      L-type Ca(2+) channel inhibitor, nifedipine (10 muM), partially inhibited EST 
      agonist and EST-induced increase in phosphorylated ERK expression. The 
      mitogen-activated protein kinase inhibitor, PD98059 (5 muM), partially prevented 
      ER agonists and EST from providing neuroprotection to TNF-alpha toxicity. Presence of 
      the nuclear ER antagonist, ICI 182 780 (10 muM), blocked the neuroprotection 
      provided by all three ER agonists tested. Taken together, our data indicate that 
      both ERalpha and ERbeta contribute to PPT, DPN, or EST-mediated neuroprotection with 
      similar signaling profiles. Our data strongly imply that PPT, DPN, or EST can be 
      used as effective neuroprotective agents to attenuate motoneuron death in ALS and 
      SCI.
FAU - Das, Arabinda
AU  - Das A
AD  - Department of Neurosciences, Medical University of South Carolina, 96 Jonathan 
      Lucas Street, Charleston, South Carolina 29425, USA.
FAU - Smith, Joshua A
AU  - Smith JA
FAU - Gibson, Cameron
AU  - Gibson C
FAU - Varma, Abhay K
AU  - Varma AK
FAU - Ray, Swapan K
AU  - Ray SK
FAU - Banik, Naren L
AU  - Banik NL
LA  - eng
GR  - NS-41088/NS/NINDS NIH HHS/United States
GR  - R01 NS031622/NS/NINDS NIH HHS/United States
GR  - R01 NS045967/NS/NINDS NIH HHS/United States
GR  - NS-45967/NS/NINDS NIH HHS/United States
GR  - C06 RR015455/RR/NCRR NIH HHS/United States
GR  - C06 RRO15455/PHS HHS/United States
GR  - NS-31622/NS/NINDS NIH HHS/United States
GR  - R01 NS041088/NS/NINDS NIH HHS/United States
GR  - R01 NS057811/NS/NINDS NIH HHS/United States
GR  - NS-57811/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20101110
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (2,3-bis(4-hydroxyphenyl)-propionitrile)
RN  - 0 (Biomarkers)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Estrogens)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nitriles)
RN  - 0 (Phenols)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0T83Y6JZPF (4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Biomarkers/metabolism
MH  - Calcium Channels, L-Type/metabolism
MH  - Cell Death/drug effects
MH  - Cell Fusion
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Embryo, Mammalian/cytology
MH  - Estrogens/*pharmacology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Hybrid Cells/metabolism
MH  - Motor Neurons/*drug effects
MH  - Neuroblastoma/pathology
MH  - Neuroprotective Agents/pharmacology
MH  - Nitriles/pharmacology
MH  - Phenols/pharmacology
MH  - Phosphorylation/drug effects
MH  - Pyrazoles/pharmacology
MH  - Rats
MH  - Receptors, Estrogen/*agonists
MH  - Signal Transduction/drug effects
MH  - Spinal Cord/embryology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC3951893
MID - NIHMS558513
COIS- Declaration of interest The authors declare that there is no conflict of interest 
      that may be perceived as prejudicing the impartiality of the research reported.
EDAT- 2010/11/12 06:00
MHDA- 2011/02/18 06:00
PMCR- 2014/03/13
CRDT- 2010/11/12 06:00
PHST- 2010/11/12 06:00 [entrez]
PHST- 2010/11/12 06:00 [pubmed]
PHST- 2011/02/18 06:00 [medline]
PHST- 2014/03/13 00:00 [pmc-release]
AID - JOE-10-0338 [pii]
AID - 10.1677/JOE-10-0338 [doi]
PST - ppublish
SO  - J Endocrinol. 2011 Feb;208(2):171-82. doi: 10.1677/JOE-10-0338. Epub 2010 Nov 10.