Please use this identifier to cite or link to this item:
|標題:||Berberine induces heme oxygenase-1 up-regulation through phosphatidylinositol 3-kinase/AKT and NF-E2-related factor-2 signaling pathway in astrocytes||作者:||Chen, J.H.
|關鍵字:||Berberine;Chinese herb;Heme oxygenase-1;Nrf2;Astrocytes;smooth-muscle-cells;suppresses neuroinflammatory responses;activated;protein-kinases;transcription factor;endothelial-cells;oxidative;stress;bv-2 microglia;nitric-oxide;lung injury;factor-i||Project:||International Immunopharmacology||期刊/報告no：:||International Immunopharmacology, Volume 12, Issue 1, Page(s) 94-100.||摘要:||
Our previous report has shown that berberine effectively inhibits LPS- and IFN-gamma-induced neuroinflammation in microglia cells. Recently, we also reported that HO-1 (Heme oxygenase-1) may be a therapeutic target to regulate neuroinflammation in microglia cells. The present study examined the ability of berberine, the major constituents of Chinese herb Rhizoma coptidis, to induce expression of HO-1, and analyzed its signaling mechanism in rat brain astrocytes. HO-1 is known as an antioxidant enzyme which helps to protect against cellular damage and maintains tissue homeostasis. Here, we found that berberine increased HO-1 mRNA and protein expression concentration- and time-dependently. In addition, berberine-induced HO-1 expression was attenuated by PI 3-kinase (phosphatidylinositol 3-kinase) inhibitors LY294002 and wortmannin, and an AKT inhibitor. Treatment of astrocytes with berberine also induced p85 (PI 3-kinase) and AKT phospholation, and increased AKT kinase activity. Berberine also increased NF-E2-related factor-2 (Nrf2) accumulation in the nucleus and increased Nrf2-DNA binding activity as determined by the EMSA (electrophoretic mobility shift assay). Moreover, berberine-induced increase of Nrf2-DNA binding activity was reduced by PI 3-kinase and AKT inhibitors. Berberine-increased HO-1-luciferase activity was also inhibited by co-transfection with dominant-negative (DN) mutants of p85 and AKT. Moreover, berberine-mediated increase of HO-1 transcriptional activity and protein expression were reduced by transfection with siRNA againt Nrf2. These findings suggest that berberine-increased HO-I expression is mediated by Nrf2 activation through the PI 3-kinase/AKT pathway in astrocytes. Thus, berberine may be useful as a therapeutic agent for the treatment of neuroinflammation-associated disorders. (C) 2011 Elsevier B.V. All rights reserved.
|Appears in Collections:||期刊論文|
Show full item record
TAIR Related Article
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.