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Dual TNF alpha-Indu...
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Correa, FernandoGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
(författare)
Dual TNF alpha-Induced Effects on NRF2 Mediated Antioxidant Defence in Astrocyte-Rich Cultures: Role of Protein Kinase Activation
- Artikel/kapitelEngelska2012
Förlag, utgivningsår, omfång ...
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2012-09-02
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Springer Science and Business Media LLC,2012
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LIBRIS-ID:oai:gup.ub.gu.se/168804
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https://gup.ub.gu.se/publication/168804URI
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https://doi.org/10.1007/s11064-012-0878-yDOI
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Tumor necrosis factor-alpha (TNF alpha) is a pleiotropic molecule that can have both protective and detrimental effects in neurodegeneration. Here we have investigated the temporal effects of TNF alpha on the inducible Nrf2 system in astrocyte-rich cultures by determination of glutathione (GSH) levels, gamma glutamylcysteine ligase (gamma GCL) activity, the protein levels of Nrf2, Keap1, the catalytic and modulatory subunit of gamma GCL (gamma GCL-C and gamma GCL-M respectively). Astrocyte-rich cultures were exposed for 24 or 72 h to different concentrations of TNF alpha. Acute exposure (24 h) of astrocyte-rich cultures to 10 ng/mL of TNF alpha increased GSH, gamma GCL activity, the protein levels of gamma GCL-M, gamma GCL-C and Nrf2 in parallel with decreased levels of Keap1. Antioxidant responsive element (ARE)-mediated transcription was blocked by inhibitors of ERK1/2, JNK and Akt whereas inactivation of p38 and GSK3 beta further enhanced transcription. In contrast treatment with TNF alpha for 72 h decreased components of the Nrf2 system in parallel with an increase of Keap1. Stimulation of the Nrf2 system by tBHQ was intact after 24 h but blocked after 72 h treatment with TNF alpha. This down-regulation after 72 h correlated with activation of p38 MAPK and GSK3 beta, since inhibition of these signalling pathways reversed this effect. The upregulation of the Nrf2 system by TNF alpha (24 h treatment) protected the cells from oxidative stress through elevated gamma GCL activity whereas the down-regulation (72 h treatment) caused pronounced oxidative toxicity. One of the important implications of the results is that in a situation where Nrf2 is decreased, such as in Alzheimer's disease, the effect of TNF alpha is detrimental.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Mallard, Carina,1963Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xmallc
(författare)
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Nilsson, Michael,1962Gothenburg 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(Swepub:gu)xnimic
(författare)
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Sandberg, Mats,1953Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xsamat
(författare)
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Göteborgs universitetInstitutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Neurochemical Research: Springer Science and Business Media LLC37:12, s. 2842-28550364-31901573-6903
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