AIM： To study the role of advanced glycation end products （AGE） and their specific receptor （RAGE） in the pathogenesis of liver fibrogenesis. METHODS： In vitro RAGE expression and extracellular matrix-related ge...AIM： To study the role of advanced glycation end products （AGE） and their specific receptor （RAGE） in the pathogenesis of liver fibrogenesis. METHODS： In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells （HSC） were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin （AGE- BSA） and N＇-（carboxymethyl） lysine （CML）-BSA, or with tumor necrosis factor-α （TNF-α）. In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS： In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α.RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1（ I ） mRNA by AGE-BSA. CONCLUSION： Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.展开更多
We studied the first oxidation product of vitamin C, the dehydro-L-ascorbic acid dimer and characterized it by infrared and Raman spectroscopies in the solid phase. The Density functional theory was used to study its ...We studied the first oxidation product of vitamin C, the dehydro-L-ascorbic acid dimer and characterized it by infrared and Raman spectroscopies in the solid phase. The Density functional theory was used to study its structure and vibrational properties. These calculations gave us a precise knowledge of the normal modes of vibration taking into account that the molecule comprises a system of five fused rings; non planar γ-lactone and furonose rings are attached to a central dioxan ring in the twisted boat conformation. The calculated harmonic vibrational frequencies are consistent with the experimental vibrational spectra. An assignment of the observed spectral features is proposed. The shift of the band located in the infrared spectrum of the ascorbic acid from 3409 cm^-1 to 3299 cml and the remarkable increase in the band intensity at 1784 cm^-1 evidences the acid decomposition into its first product, the dehydro-L-ascorbic acid. The theoretical vibrational calculations allowed us to obtain a set of scaled force constants. The nature of the different -γ-lactone, furanose and dioxan rings and their topological properties were investigated by means of natural bond orbital and Bader＇s atoms in the molecule theory, respectively.展开更多
基金Supported by Grants from the Interdisciplinary Center for Clinical Research(IZKF,Project B39)the Johannes and Frieda Marohn Foundation of the University of Erlangen-Nuremberg,Germany
文摘AIM： To study the role of advanced glycation end products （AGE） and their specific receptor （RAGE） in the pathogenesis of liver fibrogenesis. METHODS： In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells （HSC） were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin （AGE- BSA） and N＇-（carboxymethyl） lysine （CML）-BSA, or with tumor necrosis factor-α （TNF-α）. In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS： In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α.RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1（ I ） mRNA by AGE-BSA. CONCLUSION： Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.
文摘We studied the first oxidation product of vitamin C, the dehydro-L-ascorbic acid dimer and characterized it by infrared and Raman spectroscopies in the solid phase. The Density functional theory was used to study its structure and vibrational properties. These calculations gave us a precise knowledge of the normal modes of vibration taking into account that the molecule comprises a system of five fused rings; non planar γ-lactone and furonose rings are attached to a central dioxan ring in the twisted boat conformation. The calculated harmonic vibrational frequencies are consistent with the experimental vibrational spectra. An assignment of the observed spectral features is proposed. The shift of the band located in the infrared spectrum of the ascorbic acid from 3409 cm^-1 to 3299 cml and the remarkable increase in the band intensity at 1784 cm^-1 evidences the acid decomposition into its first product, the dehydro-L-ascorbic acid. The theoretical vibrational calculations allowed us to obtain a set of scaled force constants. The nature of the different -γ-lactone, furanose and dioxan rings and their topological properties were investigated by means of natural bond orbital and Bader＇s atoms in the molecule theory, respectively.
