PMID- 18160224
OWN - NLM
STAT- MEDLINE
DCOM- 20080415
LR  - 20181113
IS  - 0306-4522 (Print)
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 151
IP  - 2
DP  - 2008 Jan 24
TI  - Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese 
      superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: 
      an insight into the role of glial cells.
PG  - 622-9
AB  - Tumor necrosis factor-alpha (TNF-alpha), a ubiquitous pro-inflammatory cytokine, 
      is an important mediator in the immune-neuroendocrine system that affects the 
      CNS. The present study demonstrates that treatment with TNF-alpha activates 
      microglia to increase TNF-alpha production in primary cultures of glial cells 
      isolated from wild-type (WT) mice and mice deficient in the inducible form of 
      nitric oxide synthase (iNOSKO). However, mitochondrial dysfunction in WT neurons 
      occurs at lower concentrations of TNF-alpha when neurons are directly treated 
      with TNF-alpha or co-cultured with TNF-alpha-treated microglia than iNOSKO 
      neurons similarly treated. Immunofluorescent staining of primary neurons 
      co-cultured with TNF-alpha-treated microglia reveals that the antioxidant enzyme 
      in mitochondria, manganese superoxide dismutase (MnSOD), is co-localized with 
      nitrotyrosine in WT but not in iNOSKO primary neuronal cells. Importantly, the 
      percentage of surviving neurons is significantly reduced in WT neurons compared 
      with iNOSKO neurons under identical treatment conditions. Together, the results 
      suggest that TNF-alpha activates microglia to produce high levels of TNF-alpha 
      and that production of nitric oxide (NO) in neurons is an important factor 
      affecting MnSOD nitration and subsequent mitochondrial dysfunction.
FAU - Tangpong, J
AU  - Tangpong J
AD  - School of Allied Health Sciences and Public Health, Walailak University, Nakhon 
      Si Thammarat, 80160, Thailand. njibjoy@yahoo.com
FAU - Sompol, P
AU  - Sompol P
FAU - Vore, M
AU  - Vore M
FAU - St Clair, W
AU  - St Clair W
FAU - Butterfield, D A
AU  - Butterfield DA
FAU - St Clair, D K
AU  - St Clair DK
LA  - eng
GR  - CA94853/CA/NCI NIH HHS/United States
GR  - CA-80152/CA/NCI NIH HHS/United States
GR  - P01 AG005119/AG/NIA NIH HHS/United States
GR  - AG-05119/AG/NIA NIH HHS/United States
GR  - R01 CA094853/CA/NCI NIH HHS/United States
GR  - P01 AG005119-21/AG/NIA NIH HHS/United States
GR  - R01 CA080152/CA/NCI NIH HHS/United States
GR  - R01 CA094853-05/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20071113
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Nitrates)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EUY85H477I (thiazolyl blue)
SB  - IM
MH  - Animals
MH  - Cell Death/genetics/physiology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria/*physiology
MH  - Neuroglia/*physiology
MH  - Neurons/*metabolism
MH  - Nitrates/*metabolism
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase Type II/biosynthesis/genetics
MH  - Superoxide Dismutase/*metabolism
MH  - Tetrazolium Salts
MH  - Thiazoles
MH  - Tumor Necrosis Factor-alpha/*physiology
MH  - Tyrosine/analogs & derivatives/metabolism
PMC - PMC3437053
MID - NIHMS39189
EDAT- 2007/12/28 09:00
MHDA- 2008/04/16 09:00
PMCR- 2012/09/08
CRDT- 2007/12/28 09:00
PHST- 2007/07/12 00:00 [received]
PHST- 2007/10/17 00:00 [revised]
PHST- 2007/10/31 00:00 [accepted]
PHST- 2007/12/28 09:00 [pubmed]
PHST- 2008/04/16 09:00 [medline]
PHST- 2007/12/28 09:00 [entrez]
PHST- 2012/09/08 00:00 [pmc-release]
AID - S0306-4522(07)01336-X [pii]
AID - 10.1016/j.neuroscience.2007.10.046 [doi]
PST - ppublish
SO  - Neuroscience. 2008 Jan 24;151(2):622-9. doi: 10.1016/j.neuroscience.2007.10.046. 
      Epub 2007 Nov 13.