| Summary: | 碩士 === 國立陽明大學 === 生化暨分子生物研究所 === 97 === β2-glycoprotein Ι (β2-GPI) is a plasma glycoprotein primarily synthesized in the liver.
β2-GPI has been implicated in blood coagulation, triglyceride metabolism, antiphospholipid syndrome and atherosclerosis. However, the factors that influence β2-GPI expression still remain unclear. In this study, the effects of hydrogen peroxide on β2-GPI expression in Huh7 and its underlying mechanisms were investigated. The levels of β2-GPI mRNA, protein expression and protein secretion were increased in a dose-dependent manner after hydrogen peroxide stimulation. Numerous studies indicate that activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) can be activated by oxidative stress. We found three putative AP-1 cis-elements located between -2207 and -2063, and one putative NF-κB cis-element at the region from -1432 to -1419 of the human β2-GPI promoter. Western blot analysis showed that hydrogen peroxide induced nuclear translocation of AP-1 and NF-κB. In addition, electrophoretic mobility shift assay revealed that hydrogen peroxide enhanced the binding of nuclear extracts to AP1-2 (-2150/-2124)、AP1-3 (-2087/-2062) and NF-κB (-1438/-1413). The promoter activity of β2-GPI gene which contains AP-1 and NF-κB cis-elements were raised by hydrogen peroxide stimulation. Taken together, these results suggest that hydrogen peroxide induced β2-GPI transcription activity in Huh7 via activation of AP-1 and NF-κB. This study provide an important clue in extend insights into the regulatory mechanisms of the β2-GPI gene expression.
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