To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we establishe...To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8- and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H2O2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H2O2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.展开更多
Artemisinin-typed endoperoxides are a promising novel class of antischistosomal agents. Their antischistosomal activity is associated with high levels of intraceca toxic heme, which catalyzes the cleavage of the endop...Artemisinin-typed endoperoxides are a promising novel class of antischistosomal agents. Their antischistosomal activity is associated with high levels of intraceca toxic heme, which catalyzes the cleavage of the endoperoxide bridge to generate free radicals followed by such membrane damages as lipid peroxidation and protein denaturation. The interaction of the endoperoxides with heme also enhances heme-induced membrane toxicity by way of stimulating the redox activity of heme and preventing its polymerization to chemically inert pigment. Moreover, the drug-derivative radicals may disturb the parasites prooxidant-antioxidant balance, thereby sensitizing them to subsequent lethal damages of endogenous and exogenous oxidants increase. The free radicals-mediated mode of action of the endoperoxides may be used to explain such phenomena as sex difference and developmental stage difference in susceptibility to the endoperoxides as well as their slow schistosome killing.展开更多
采用薄膜旋转蒸发-超声法分别制备了柠檬酸铁脂质体(FAC-Lip)和血红素铁脂质体(Heme-Lip).通过测定铁脂质体的体外释放,发现两种铁脂质体均具有缓释性,并且Heme-Lip的缓释性比FAC-Lip的好;采用平衡透析法测定了脂质体/水分配系数(P),并...采用薄膜旋转蒸发-超声法分别制备了柠檬酸铁脂质体(FAC-Lip)和血红素铁脂质体(Heme-Lip).通过测定铁脂质体的体外释放,发现两种铁脂质体均具有缓释性,并且Heme-Lip的缓释性比FAC-Lip的好;采用平衡透析法测定了脂质体/水分配系数(P),并考察影响分配系数的因素,初步探讨了FAC和Heme与脂质体膜结合的吉布斯自由能(ΔG),结果发现随着胆固醇含量和药脂比例的增加,P先增大后减小,当P最大时,药物与磷脂膜的氢键及静电作用力最大;在透析平衡时,计算得到了FAC-Lip和Heme-Lip中药物与脂质体膜层之间的吉布斯自由能分别为–12.7和–18.2 k J mol–1.展开更多
基金This work was kindly supported by Na-tional Natural Science Foundation of China(No.39670308)
文摘To investigate whether the expression of exogenous heme oxygenase-1 (HO-1) gene within vascular smooth muscle cells (VSMC) could protect the cells from free radical attack and inhibit cell proliferation, we established an in vitro transfection of human HO-1 gene into rat VSMC mediated by a retroviral vector. The results showed that the profound expression of HO-1 protein as well as HO activity was 1.8- and 2.0-fold increased respectively in the transfected cells compared to the non-transfected ones. The treatment of VSMC with different concentrations of H2O2 led to the remarkable cell damage as indicated by survival rate and LDH leakage. However, the resistance of the HO-1 transfected VSMC against H2O2 was significantly raised. This protective effect was dramatically diminished when the transfected VSMC were pretreated with ZnPP-IX, a specific inhibitor of HO, for 24 h. In addition, we found that the growth potential of the transfected cells was significantly inhibited directly by increased activity of HO-1, and this effect might be related to decreased phosphorylation of MAPK. These results suggest that the overexpression of introduced hHO-1 is potentially able to reduce the risk factors of atherosclerosis, partially due to its cellular protection against oxidative injury and to its inhibitory effect on cellular proliferation.
文摘Artemisinin-typed endoperoxides are a promising novel class of antischistosomal agents. Their antischistosomal activity is associated with high levels of intraceca toxic heme, which catalyzes the cleavage of the endoperoxide bridge to generate free radicals followed by such membrane damages as lipid peroxidation and protein denaturation. The interaction of the endoperoxides with heme also enhances heme-induced membrane toxicity by way of stimulating the redox activity of heme and preventing its polymerization to chemically inert pigment. Moreover, the drug-derivative radicals may disturb the parasites prooxidant-antioxidant balance, thereby sensitizing them to subsequent lethal damages of endogenous and exogenous oxidants increase. The free radicals-mediated mode of action of the endoperoxides may be used to explain such phenomena as sex difference and developmental stage difference in susceptibility to the endoperoxides as well as their slow schistosome killing.
文摘采用薄膜旋转蒸发-超声法分别制备了柠檬酸铁脂质体(FAC-Lip)和血红素铁脂质体(Heme-Lip).通过测定铁脂质体的体外释放,发现两种铁脂质体均具有缓释性,并且Heme-Lip的缓释性比FAC-Lip的好;采用平衡透析法测定了脂质体/水分配系数(P),并考察影响分配系数的因素,初步探讨了FAC和Heme与脂质体膜结合的吉布斯自由能(ΔG),结果发现随着胆固醇含量和药脂比例的增加,P先增大后减小,当P最大时,药物与磷脂膜的氢键及静电作用力最大;在透析平衡时,计算得到了FAC-Lip和Heme-Lip中药物与脂质体膜层之间的吉布斯自由能分别为–12.7和–18.2 k J mol–1.
