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The Nrf2-inducible ...
The Nrf2-inducible antioxidant defense in astrocytes can be both up- and down-regulated by activated microglia:Involvement of p38 MAPK.
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- Correa, Fernando (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Ljunggren, Elin (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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- Mallard, Carina, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Nilsson, Michael, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
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Weber, Stephen G (author)
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- Sandberg, Mats, 1953 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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(creator_code:org_t)
- 2011-02-23
- 2011
- English.
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In: Glia. - : Wiley. - 1098-1136 .- 0894-1491. ; 59:5, s. 785-99
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Abstract
Subject headings
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- The effects of microglia-conditioned medium (MCM) on the inducible Nrf2 system in astrocyte-rich cultures were investigated by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the modulatory subunit of γGCL (γGCL-M) and activated MAP kinases (ERK1/2, JNK and p38). Microglia were either cultured for 24 h in serum-free culture medium to achieve microglia-conditioned medium from non-activated cells (MCM(0) ), used as control condition, or activated with different concentrations (0.1-1,000 ng mL(-1) ) of lipopolysaccharide (LPS) to produce MCM(0.1-1,000) . Acute exposure (24 h) to MCM(100) increased GSH, γGCL activity, the protein levels of γGCL-M, Nrf2, and activated JNK and ERK1/2 in astrocyte-rich cultures. In contrast, treatment with MCM(10) for 24 h decreased components of the Nrf2 system in parallel with activation of p38 MAPK. Stimulation of the Nrf2 system by tBHQ was partly intact after 24 h but blocked after 72 h treatment with MCM(10) and MCM(100) . This down-regulation after 72 h correlated with activation of p38 MAPK and lack of ERK1/2 and JNK activation. The negative effects were partly reversed by an inhibitor of p38 which restored tBHQ mediated protection against oxidative stress. In conclusion, the study showed a negative effect of MCM(10) on the inducible anti-oxidant defense in astrocyte-rich cultures at both 24 and 72 h that correlated with activation of p38 and was partly reversed by a p38 inhibitor. A transient protective effect of MCM(100) on astrocyte-rich cultures against H(2)O(2) toxicity was observed at 24 h which coincided with activation of JNK and ERK1/2.
Keyword
- Analysis of Variance
- Animals
- Animals
- Newborn
- Astrocytes
- cytology
- drug effects
- immunology
- metabolism
- Blotting
- Western
- Cell Survival
- physiology
- Cells
- Cultured
- Cerebral Cortex
- cytology
- drug effects
- metabolism
- Culture Media
- Conditioned
- Down-Regulation
- drug effects
- physiology
- Extracellular Signal-Regulated MAP Kinases
- metabolism
- Glutathione
- metabolism
- Hydroquinones
- pharmacology
- JNK Mitogen-Activated Protein Kinases
- metabolism
- Microglia
- cytology
- drug effects
- immunology
- metabolism
- NF-E2-Related Factor 2
- metabolism
- Oxidative Stress
- drug effects
- physiology
- Rats
- Rats
- Sprague-Dawley
- Up-Regulation
- drug effects
- physiology
- p38 Mitogen-Activated Protein Kinases
- metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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