Inhibitory effect of a tyrosine-fructose Maillard reaction product, 2,4-bis(p-hydroxyphenyl)-2-butenal on amyloid-beta generation and inflammatory reactions via inhibition of NF-kappa B and STAT3 activation in cultured astrocytes and microglial BV-2 cells

Title
Inhibitory effect of a tyrosine-fructose Maillard reaction product, 2,4-bis(p-hydroxyphenyl)-2-butenal on amyloid-beta generation and inflammatory reactions via inhibition of NF-kappa B and STAT3 activation in cultured astrocytes and microglial BV-2 cells
Author(s)
최동영이영중[이영중]최임섭[최임섭]한진이[한진이]정헌상[정헌상]한상배[한상배]오기완[오기완]홍진태[홍진태]
Keywords
NITRIC-OXIDE SYNTHASE; PRECURSOR PROTEIN GENE; NECROSIS-FACTOR-ALPHA; B/REL BINDING-SITE; ALZHEIMERS-DISEASE; ANTIOXIDANT ACTIVITY; BACE1 PROMOTER; REGULATORY REGION; MOUSE MODEL; EXPRESSION
Issue Date
201110
Publisher
BIOMED CENTRAL LTD
Citation
JOURNAL OF NEUROINFLAMMATION, v.8
Abstract
Background: Amyloidogenesis is linked to neuroinflammation. The tyrosine-fructose Maillard reaction product, 2,4-bis(p-hydroxyphenyl)-2-butenal, possesses anti-inflammatory properties in cultured macrophages, and in an arthritis animal model. Because astrocytes and microglia are responsible for amyloidogenesis and inflammatory reactions in the brain, we investigated the anti-inflammatory and anti-amyloidogenic effects of 2,4-bis(p-hydroxyphenyl)-2-butenal in lipopolysaccharide (LPS)-stimulated astrocytes and microglial BV-2 cells. Methods: Cultured astrocytes and microglial BV-2 cells were treated with LPS (1 mu g/ml) for 24 h, in the presence (1, 2, 5 mu M) or absence of 2,4-bis(p-hydroxyphenyl)-2-butenal, and harvested. We performed molecular biological analyses to determine the levels of inflammatory and amyloid-related proteins and molecules, cytokines, Ab, and secretases activity. Nuclear factor-kappa B (NF-kappa B) DNA binding activity was determined using gel mobility shift assays. Results: We found that 2,4-bis(p-hydroxyphenyl)-2-butenal (1, 2, 5 mu M) suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) in LPS (1 mu g/ml)-stimulated astrocytes and microglial BV-2 cells. Further, 2,4-bis(p-hydroxyphenyl)-2-butenal inhibited the transcriptional and DNA binding activity of NF-kappa B-alpha transcription factor that regulates genes involved in neuroinflammation and amyloidogenesis via inhibition of I kappa B degradation as well as nuclear translocation of p50 and p65. Consistent with the inhibitory effect on inflammatory reactions, 2,4-bis(p-hydroxyphenyl)-2-butenal inhibited LPS-elevated A beta(42) levels through attenuation of beta- and gamma-secretase activities. Moreover, studies using signal transducer and activator of transcription 3 (STAT3) siRNA and a pharmacological inhibitor showed that 2,4-bis(p-hydroxyphenyl)-2-butenal inhibits LPS-induced activation of STAT3. Conclusions: These results indicate that 2,4-bis(p-hydroxyphenyl)-2-butenal inhibits neuroinflammatory reactions and amyloidogenesis through inhibition of NF-kappa B and STAT3 activation, and suggest that 2,4-bis(p-hydroxyphenyl)2-butenal may be useful for the treatment of neuroinflammatory diseases like Alzheimer's disease.
URI
http://hdl.handle.net/YU.REPOSITORY/24404http://dx.doi.org/10.1186/1742-2094-8-132
ISSN
1742-2094
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약학대학 > 약학부 > Articles
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