PMID- 12230306
OWN - NLM
STAT- MEDLINE
DCOM- 20030206
LR  - 20181113
IS  - 1535-1084 (Print)
IS  - 1535-1084 (Linking)
VI  - 2
IP  - 1
DP  - 2002
TI  - Methamphetamine-induced TNF-alpha gene expression and activation of AP-1 in 
      discrete regions of mouse brain: potential role of reactive oxygen intermediates 
      and lipid peroxidation.
PG  - 71-85
AB  - Cellular and molecular mechanisms of methamphetamine (METH)-induced neurotoxicity 
      may involve alterations of cellular redox status and induction of inflammatory 
      genes. To study this hypothesis, molecular signaling pathways of METH-induced 
      inflammatory responses via activation of redox-sensitive transcription factors 
      were investigated in discrete regions (corpus striatum, frontal cortex, and 
      hippocampus) of mouse brain. Intraperitoneal injection of METH at a dose of 10 
      mg/kg body weight resulted in a significant increase in oxidative stress, as 
      measured by 2,7-dichlorofluorescein (DCF) fluorescence assay, thiobarbituric 
      acid-reactive substances (TBARS), and total glutathione levels. Glutathione 
      peroxidase activity was also significantly increased after METH exposure. In 
      addition, DNA binding activity of activator protein-1 (AP-1), a redox-responsive 
      transcription factor, was increased in all studied brain regions in response to 
      METH treatment. Because AP-1 is known to regulate expression of inflammatory 
      genes, levels of TNF-alpha mRNA were also studied. Expression of the tumor 
      necrosis factor-alpha (TNF-alpha) gene was induced 3 h after METH injection and 
      remained elevated for up to 6 h of METH exposure. In addition, stimulation of the 
      TNF-alpha gene was associated with increased TNF-a protein production in the 
      frontal cortex. These results suggest that METH-induced disturbances in cellular 
      redox status and that activation of AP-1 can play a critical role in signaling 
      pathways leading to upregulation of inflammatory genes in vivo. Furthermore, 
      these data provide evidence for the role of oxidative stress in the neurotoxic 
      effects of METH.
FAU - Flora, Govinder
AU  - Flora G
AD  - Departments of Surgery, University of Kentucky, Lexington 40536, USA.
FAU - Lee, Yong Woo
AU  - Lee YW
FAU - Nath, Avindra
AU  - Nath A
FAU - Maragos, William
AU  - Maragos W
FAU - Hennig, Bernhard
AU  - Hennig B
FAU - Toborek, Michal
AU  - Toborek M
LA  - eng
GR  - P42 ES007380/ES/NIEHS NIH HHS/United States
GR  - MH63022/MH/NIMH NIH HHS/United States
GR  - NS39254/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neuromolecular Med
JT  - Neuromolecular medicine
JID - 101135365
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Dopamine Agents)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 44RAL3456C (Methamphetamine)
RN  - 9007-49-2 (DNA)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - Brain Chemistry/*drug effects
MH  - Central Nervous System Stimulants/administration & dosage/*pharmacology/toxicity
MH  - Corpus Striatum/drug effects/metabolism
MH  - DNA/genetics/metabolism
MH  - Dopamine Agents/administration & dosage/*pharmacology/toxicity
MH  - Frontal Lobe/drug effects/metabolism
MH  - Glutathione/analysis
MH  - Glutathione Peroxidase/metabolism
MH  - Hippocampus/drug effects/metabolism
MH  - Inflammation/genetics
MH  - Injections, Intraperitoneal
MH  - Lipid Peroxidation/drug effects
MH  - Male
MH  - Methamphetamine/administration & dosage/*pharmacology/toxicity
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Oxidative Stress
MH  - Signal Transduction/drug effects
MH  - Thiobarbituric Acid Reactive Substances/analysis
MH  - Transcription Factor AP-1/*metabolism
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/genetics
EDAT- 2002/09/17 10:00
MHDA- 2003/02/07 04:00
CRDT- 2002/09/17 10:00
PHST- 2002/09/17 10:00 [pubmed]
PHST- 2003/02/07 04:00 [medline]
PHST- 2002/09/17 10:00 [entrez]
AID - NMM:2:1:71 [pii]
AID - 10.1385/NMM:2:1:71 [doi]
PST - ppublish
SO  - Neuromolecular Med. 2002;2(1):71-85. doi: 10.1385/NMM:2:1:71.