AIM: Heme oxygenase (HO)-I catalyzes the conversion of heme to biliverdin, iron and carbon monoxide. HO-1 is induced by many stimuli including heme, Hb, heat stress,lipopolysaccharide (LP5) and cytokines. Previous stu...AIM: Heme oxygenase (HO)-I catalyzes the conversion of heme to biliverdin, iron and carbon monoxide. HO-1 is induced by many stimuli including heme, Hb, heat stress,lipopolysaccharide (LP5) and cytokines. Previous studies demonstrated that LP5 induced HO-1 gene activation and HO-1 expression in liver. However, the mechanisms of LPS-induced HO-1 expression in liver remain unknown. The effect of toll-like receptor-4 (TLR4) on LPS-induced liver HO-1 expression and the role of TNF-α and IL-1β in this condition were determined.METHODS: HO-1 expression was determined by immunofluorescent staining and immunoblotting. Double immunofluorescent staining was performed to determine the cell type of HO-1 expression in liver.RESULTS: A low dose of LPS significantly increased HO-1 expression in the liver which was localized in Kupffer cells only. Furthermore, HO-1 expression was enhanced by three doses of LPS. HO-1 expression was significantly inhibited in the liver of TLR4 mutant mice. While the liver HO-1 expression in TNF KO mice was much lower than that in C57 mice following the same LPS treatment, IL-1β KO had a slight influence on liver HO-1 expression following LPS treatment.CONCLUSION: The preserfl: results confirm that macrophages are the major source of HO-1 in the liver induced by LPS.This study demonstrates that TLR4 plays a dominant role in mediating HO-1 expression following LPS. LPS-induced HO-1 expression is mainly mediated by endogenous TNF-α, but only partially by endogenous IL-1β.展开更多
AIM: Activated pancreatic stellate cells (PSCs) are implicated in the pathogenesis of pancreatic inflammation and fibrosis,where oxidative stress is thought to play a key role. 4-hydroxy-2,3-nonenal (HNE) is generated...AIM: Activated pancreatic stellate cells (PSCs) are implicated in the pathogenesis of pancreatic inflammation and fibrosis,where oxidative stress is thought to play a key role. 4-hydroxy-2,3-nonenal (HNE) is generated endogenously during the process of lipid peroxidation, and has been accepted as a mediator of oxidative stress. The aim of this study was to clarify the effects of HNE on the activation of signal transduction pathways and cellular functions in PSCs.METHODS: PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase P, and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. PSCs were treated with physiologically relevant and non-cytotoxic concentrations (up to 5 μmol/L) of HNE. Activation of transcription factors was examined by electrophoretic mobility shift assay and luciferase assay.Activation of mitogen-activated protein (MAP) kinases was assessed by Western blotting using anti-phosphospecific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Production of type Ⅰ collagen and monocyte chemoattractant protein-1 was determined by enzyme-linked immunosorbent assay.The effect of HNE on the transformation of freshly isolated PSCs in culture was also assessed.RESULTS: HNE activated activator protein-1, but not nuclear factor KB. In addition, HNE activated three classes of MAP kinases: extrcellular signal-regulated kinase, c-jun N-terminal kinase, and p38 MAP kinase. HNE increased type I collagen production through the activation of p38 MAP kinase and c-jun N-terminal kinase. HNE did not alter the proliferation,or monocyte chemoattractant protein-1 production. HNE did not initiate the transformation of freshly isolated PSCs to myofibroblast-like phenotype.CONCLUSION: Spedflc activation of these signal transduction pathways and altered cell functions such as collagen production by HNE may play a role in the pathogenesis of pancreatic disorders.展开更多
The improvement on the calculation of anti-Stokes energy transfer rate is studied in the present work. The additional proportion coefficient between Stokes and anti-Stokes light intensities of quantum Raman scattering...The improvement on the calculation of anti-Stokes energy transfer rate is studied in the present work. The additional proportion coefficient between Stokes and anti-Stokes light intensities of quantum Raman scattering theory as compared with the classical Raman theory is introduced to successfully describe the anti-Stokes energy transfer. The theoretical formula for the improvement on the calculation of anti-Stokes energy transfer rate is derived for the first time in this study. The correctness of introducing coefficient exp{△E/kT} from well-known Raman scatter theory is demonstrated also. Moreover, the experimental lifetime measurement in Er0.01YbxY1-0.01-xVO4 crystal is performed to justify the validity of our important improvement in the original phonon-assisted energy transfer theory for the first time.展开更多
文摘AIM: Heme oxygenase (HO)-I catalyzes the conversion of heme to biliverdin, iron and carbon monoxide. HO-1 is induced by many stimuli including heme, Hb, heat stress,lipopolysaccharide (LP5) and cytokines. Previous studies demonstrated that LP5 induced HO-1 gene activation and HO-1 expression in liver. However, the mechanisms of LPS-induced HO-1 expression in liver remain unknown. The effect of toll-like receptor-4 (TLR4) on LPS-induced liver HO-1 expression and the role of TNF-α and IL-1β in this condition were determined.METHODS: HO-1 expression was determined by immunofluorescent staining and immunoblotting. Double immunofluorescent staining was performed to determine the cell type of HO-1 expression in liver.RESULTS: A low dose of LPS significantly increased HO-1 expression in the liver which was localized in Kupffer cells only. Furthermore, HO-1 expression was enhanced by three doses of LPS. HO-1 expression was significantly inhibited in the liver of TLR4 mutant mice. While the liver HO-1 expression in TNF KO mice was much lower than that in C57 mice following the same LPS treatment, IL-1β KO had a slight influence on liver HO-1 expression following LPS treatment.CONCLUSION: The preserfl: results confirm that macrophages are the major source of HO-1 in the liver induced by LPS.This study demonstrates that TLR4 plays a dominant role in mediating HO-1 expression following LPS. LPS-induced HO-1 expression is mainly mediated by endogenous TNF-α, but only partially by endogenous IL-1β.
基金Supported by Grant-in-Aid for Encouragement of Young Scientists from Japan Society for the Promotion of Science(to A.M.),by Pancreas Research Foundation of Japan(to A.M.),and by the Kanae Foundation for Life and Socio-Medical Science(to A.M.)
文摘AIM: Activated pancreatic stellate cells (PSCs) are implicated in the pathogenesis of pancreatic inflammation and fibrosis,where oxidative stress is thought to play a key role. 4-hydroxy-2,3-nonenal (HNE) is generated endogenously during the process of lipid peroxidation, and has been accepted as a mediator of oxidative stress. The aim of this study was to clarify the effects of HNE on the activation of signal transduction pathways and cellular functions in PSCs.METHODS: PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase P, and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. PSCs were treated with physiologically relevant and non-cytotoxic concentrations (up to 5 μmol/L) of HNE. Activation of transcription factors was examined by electrophoretic mobility shift assay and luciferase assay.Activation of mitogen-activated protein (MAP) kinases was assessed by Western blotting using anti-phosphospecific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Production of type Ⅰ collagen and monocyte chemoattractant protein-1 was determined by enzyme-linked immunosorbent assay.The effect of HNE on the transformation of freshly isolated PSCs in culture was also assessed.RESULTS: HNE activated activator protein-1, but not nuclear factor KB. In addition, HNE activated three classes of MAP kinases: extrcellular signal-regulated kinase, c-jun N-terminal kinase, and p38 MAP kinase. HNE increased type I collagen production through the activation of p38 MAP kinase and c-jun N-terminal kinase. HNE did not alter the proliferation,or monocyte chemoattractant protein-1 production. HNE did not initiate the transformation of freshly isolated PSCs to myofibroblast-like phenotype.CONCLUSION: Spedflc activation of these signal transduction pathways and altered cell functions such as collagen production by HNE may play a role in the pathogenesis of pancreatic disorders.
基金supported by the National Natural Science Foundation of China (Grant No.10674019)
文摘The improvement on the calculation of anti-Stokes energy transfer rate is studied in the present work. The additional proportion coefficient between Stokes and anti-Stokes light intensities of quantum Raman scattering theory as compared with the classical Raman theory is introduced to successfully describe the anti-Stokes energy transfer. The theoretical formula for the improvement on the calculation of anti-Stokes energy transfer rate is derived for the first time in this study. The correctness of introducing coefficient exp{△E/kT} from well-known Raman scatter theory is demonstrated also. Moreover, the experimental lifetime measurement in Er0.01YbxY1-0.01-xVO4 crystal is performed to justify the validity of our important improvement in the original phonon-assisted energy transfer theory for the first time.
