DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has sho...DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has shown recent potential as a treatment for Parkinson’s disease.However,the underlying mechanism of action of NBP remains poorly understood.In this study,we established a rat model of Parkinson’s disease by intraperitoneal injection of rotenone for 28 successive days,followed by intragastric injection of NBP for 14-28 days.We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson’s disease,inhibited loss of dopaminergic neurons and aggregation ofα-synuclein,and reduced iron deposition in the substantia nigra and iron content in serum.These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor,ferritin light chain,and transferrin 1.NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson’s disease.Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition,oxidative stress,and ferroptosis in the substantia nigra.展开更多
目的:研究运动性低血色素形成中大鼠十二指肠铁转运蛋白血红素转运蛋白1(heme carrier protein 1,HCP1)、二价金属离子转运体1(divalent metal transporter1,DMT1)及膜铁转运蛋白1(ferroportin1,FPN1)表达的动态变化,探讨运动性低血色...目的:研究运动性低血色素形成中大鼠十二指肠铁转运蛋白血红素转运蛋白1(heme carrier protein 1,HCP1)、二价金属离子转运体1(divalent metal transporter1,DMT1)及膜铁转运蛋白1(ferroportin1,FPN1)表达的动态变化,探讨运动性低血色素的发生机制。方法:36只雄性Wistar大鼠随机分为对照组和运动组。运动组大鼠进行为期5周、6 d/周、坡度为0、速度30 m/min的递增负荷跑台训练。前2周每天训练1次,时间从1 min开始,每次递增2 min。从第3周开始,每天训练2次。分别于运动第3、4、5周末取材,采用血细胞自动分析仪测定血红蛋白(Hb)含量;Western Blot检测十二指肠上皮细胞HCP1、DMT1及FPN1表达。结果:(1)长时间大强度运动后大鼠Hb含量逐渐降低。运动组3周末Hb与其对照组相比有下降趋势,4周和5周末显著低于其对照组(P<0.05,P<0.01)。(2)运动组大鼠3周末小肠上皮细胞HCP1、DMT1及FPN1表达均显著高于其对照组(P<0.01),4周末与其对照组相比均无显著差异(P>0.05),5周末均显著低于对照组(P<0.01)。结论:大强度运动开始阶段,机体通过增加肠铁吸收维持运动机体对铁的需求,随运动时间延长,机体肠铁吸收能力降低,这是引发运动性低血色素的重要原因之一。展开更多
Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer＇s dis- ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese her...Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer＇s dis- ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer＇s disease patients. An APPs,~JPSI^E9 double transgenic mouse model of Alzheimer＇s disease was used. The intragas- tric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer＇s disease. These com- pounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer＇s disease.展开更多
Previous studies have shown that baicalin prevented iron accumulation after substantia nigra injury, reduced divalent metal transporter 1 expression, and increased ferroportin 1 expression in the substantia nigra of r...Previous studies have shown that baicalin prevented iron accumulation after substantia nigra injury, reduced divalent metal transporter 1 expression, and increased ferroportin 1 expression in the substantia nigra of rotenone-induced Parkinson＇s disease rats. In the current study, we investigated the relationship between iron accumulation and transferrin expression in C6 cells, to explore the mechanisms of the inhibitory effect of baicalin on iron accumulation observed in Parkinson＇s disease rats. Iron content was detected using inductively coupled plasma-atomic emission spectroscopy. Results showed that iron content decreased 41% after blocking divalent metal transporter 1 and ferroportin 1 proteins. After treatment with ferric ammonium citrate of differing concentrations （10, 50, 100, 400 ktg/mL） in C6 glioma cells, cell survival rate and ferroportin 1 expression were negatively correlated with ferric ammonium citrate concentration, but divalent metal transporter 1 expression positively correlated with ferric ammonium citrate concentration. Baicalin or deferoxamine reduced divalent metal transporter 1 expression, but increased ferroportin 1 expression in the 100 μg/mL ferric ammonium citrate-loaded C6 cells. These results indicate that baicalin down-regulated iron concentration, which positively regulat- ed divalent metal transporter 1 expression and negatively regulated ferroportin 1 expression, and decreased iron accumulation in the substantia nigra.展开更多
Objective To investigate the multiple iron metabolism-related genes expression, its regulation by iron and the expression correlation among the genes in rat tissues. Methods Two groups （n=30） of Sprague-Dawley femal...Objective To investigate the multiple iron metabolism-related genes expression, its regulation by iron and the expression correlation among the genes in rat tissues. Methods Two groups （n=30） of Sprague-Dawley female weanling rats were fed with a control diet and an iron deficient diet respectively for 4 weeks. All rats were then sacrificed, and blood and tissue samples were collected. The routine blood examination was performed with a veterinary automatic blood cell analyzer. Elemental iron levels in liver, spleen and serum were determined by atomic absorption spectrophotometry. The mRNA expression of genes was detected by real-time fluorescence quantitative PCR. Results After 4 weeks, the hemoglobin （Hb） level and red blood cell （RBC） count were significantly lower in the iron deficient group compared with those in the control group. The iron levels in liver, spleen and serum in the iron deficient group were significantly lower than those in the control group. In reference to small intestine, the relative expression of each iron-related gene varied in the different tissues. Under the iron deficiency, the expression of these genes changed in a tissue-specific manner. The expression of most of the genes significantly correlated in intestine, spleen and lung, but few correlated in liver, heart and kidney. Conclusion Findings from our study provides new regulation by iron and correlation among the mRNA divalent metal transporter 1, ferritin, iron regulation protein, hepcidin, ferroportin 1 and hephaestin in intesti understandings about the relative expression, expressions of transferrin receptors 1 and 2, proteins 1 and 2, hereditary hemochromatosis ne, liver, spleen, kidney, heart, and lung of rat.展开更多
人类机体的铁代谢表现为受限制的对外界铁的吸收和有效的机体内的铁的再循环利用,单核巨噬细胞系统通过吞噬衰老的红细胞,储存和释放铁,在机体铁的循环再利用方面起到了重要的作用。因此,单核巨噬细胞系统对整个机体铁稳态的维持非常重...人类机体的铁代谢表现为受限制的对外界铁的吸收和有效的机体内的铁的再循环利用,单核巨噬细胞系统通过吞噬衰老的红细胞,储存和释放铁,在机体铁的循环再利用方面起到了重要的作用。因此,单核巨噬细胞系统对整个机体铁稳态的维持非常重要。近年来,随着转铁蛋白受体1(transferrin receptor1,TfR1)、铁蛋白(ferritin,Fn)、二价金属离子转运蛋白1(divalent metal transporter1,DMT1)、膜铁转运蛋白1(ferroportin1,FPN1),以及铁调素(hepcidin)等在单核巨噬细胞系统中功能和调控机制研究的不断深入,日益加深了人们对单核巨噬细胞系统的铁代谢过程和调控机制的了解。该文综述了铁水平、NO以及炎症等因素对单核巨噬细胞系统TfR1、Fn、DMT1、FPN1、hepcidin等蛋白表达的调控及其机制研究的最新进展。展开更多
基金funded by the National Natural Science Foundation of China, No. 81873924 (to QQL), No. 82171190 (to GHW)Nantong Science and Technology Project of China, No. MS22021010 (to LHS)High-level Innovation and Entrepreneurship Talents Introduction Program of Jiangsu Province of China (to QQL)
文摘DL-3-n-butylphthalide(NBP)-a compound isolated from Apium graveolens seeds-is protective against brain ischemia via various mechanisms in humans and has been approved for treatment of acute ischemic stroke.NBP has shown recent potential as a treatment for Parkinson’s disease.However,the underlying mechanism of action of NBP remains poorly understood.In this study,we established a rat model of Parkinson’s disease by intraperitoneal injection of rotenone for 28 successive days,followed by intragastric injection of NBP for 14-28 days.We found that NBP greatly alleviated rotenone-induced motor disturbance in the rat model of Parkinson’s disease,inhibited loss of dopaminergic neurons and aggregation ofα-synuclein,and reduced iron deposition in the substantia nigra and iron content in serum.These changes were achieved by alterations in the expression of the iron metabolism-related proteins transferrin receptor,ferritin light chain,and transferrin 1.NBP also inhibited oxidative stress in the substantia nigra and protected mitochondria in the rat model of Parkinson’s disease.Our findings suggest that NBP alleviates motor disturbance by inhibition of iron deposition,oxidative stress,and ferroptosis in the substantia nigra.
基金supported by the National Natural Science Foundation of China,No.81273983the Natural Science Foundation of Hebei Province in China,No.C2010001471+1 种基金the Scientific and Technological Research Youth Foundation of Colleges and Universities in Hebei Province of China,No.Q2012036the Hebei Provincial Food and Drug Administration in China,No.PT2014053
文摘Abnormally increased levels of iron in the brain trigger cascade amplification in Alzheimer＇s dis- ease patients, resulting in neuronal death. This study investigated whether components extracted from the Chinese herbs epimedium herb, milkvetch root and kudzuvine root could relieve the abnormal expression of iron metabolism-related protein in Alzheimer＇s disease patients. An APPs,~JPSI^E9 double transgenic mouse model of Alzheimer＇s disease was used. The intragas- tric administration of compounds from epimedium herb, milkvetch root and kudzuvine root improved pathological alterations such as neuronal edema, increased the number of neurons, downregulated divalent metal transporter 1 expression, upregulated ferroportin 1 expression, and inhibited iron overload in the cerebral cortex of mice with Alzheimer＇s disease. These com- pounds reduced iron overload-induced impairment of the central nervous system, indicating a new strategy for developing novel drugs for the treatment of Alzheimer＇s disease.
基金supported by the Scientific Research Common Program of Beijing Municipal Commission of Education,No.KM20110025010
文摘Previous studies have shown that baicalin prevented iron accumulation after substantia nigra injury, reduced divalent metal transporter 1 expression, and increased ferroportin 1 expression in the substantia nigra of rotenone-induced Parkinson＇s disease rats. In the current study, we investigated the relationship between iron accumulation and transferrin expression in C6 cells, to explore the mechanisms of the inhibitory effect of baicalin on iron accumulation observed in Parkinson＇s disease rats. Iron content was detected using inductively coupled plasma-atomic emission spectroscopy. Results showed that iron content decreased 41% after blocking divalent metal transporter 1 and ferroportin 1 proteins. After treatment with ferric ammonium citrate of differing concentrations （10, 50, 100, 400 ktg/mL） in C6 glioma cells, cell survival rate and ferroportin 1 expression were negatively correlated with ferric ammonium citrate concentration, but divalent metal transporter 1 expression positively correlated with ferric ammonium citrate concentration. Baicalin or deferoxamine reduced divalent metal transporter 1 expression, but increased ferroportin 1 expression in the 100 μg/mL ferric ammonium citrate-loaded C6 cells. These results indicate that baicalin down-regulated iron concentration, which positively regulat- ed divalent metal transporter 1 expression and negatively regulated ferroportin 1 expression, and decreased iron accumulation in the substantia nigra.
基金supported by the National Natural Science Foundation of China (No.30800909)the Fundamental Research Funds for the Central Universities
文摘Objective To investigate the multiple iron metabolism-related genes expression, its regulation by iron and the expression correlation among the genes in rat tissues. Methods Two groups （n=30） of Sprague-Dawley female weanling rats were fed with a control diet and an iron deficient diet respectively for 4 weeks. All rats were then sacrificed, and blood and tissue samples were collected. The routine blood examination was performed with a veterinary automatic blood cell analyzer. Elemental iron levels in liver, spleen and serum were determined by atomic absorption spectrophotometry. The mRNA expression of genes was detected by real-time fluorescence quantitative PCR. Results After 4 weeks, the hemoglobin （Hb） level and red blood cell （RBC） count were significantly lower in the iron deficient group compared with those in the control group. The iron levels in liver, spleen and serum in the iron deficient group were significantly lower than those in the control group. In reference to small intestine, the relative expression of each iron-related gene varied in the different tissues. Under the iron deficiency, the expression of these genes changed in a tissue-specific manner. The expression of most of the genes significantly correlated in intestine, spleen and lung, but few correlated in liver, heart and kidney. Conclusion Findings from our study provides new regulation by iron and correlation among the mRNA divalent metal transporter 1, ferritin, iron regulation protein, hepcidin, ferroportin 1 and hephaestin in intesti understandings about the relative expression, expressions of transferrin receptors 1 and 2, proteins 1 and 2, hereditary hemochromatosis ne, liver, spleen, kidney, heart, and lung of rat.
文摘人类机体的铁代谢表现为受限制的对外界铁的吸收和有效的机体内的铁的再循环利用,单核巨噬细胞系统通过吞噬衰老的红细胞,储存和释放铁,在机体铁的循环再利用方面起到了重要的作用。因此,单核巨噬细胞系统对整个机体铁稳态的维持非常重要。近年来,随着转铁蛋白受体1(transferrin receptor1,TfR1)、铁蛋白(ferritin,Fn)、二价金属离子转运蛋白1(divalent metal transporter1,DMT1)、膜铁转运蛋白1(ferroportin1,FPN1),以及铁调素(hepcidin)等在单核巨噬细胞系统中功能和调控机制研究的不断深入,日益加深了人们对单核巨噬细胞系统的铁代谢过程和调控机制的了解。该文综述了铁水平、NO以及炎症等因素对单核巨噬细胞系统TfR1、Fn、DMT1、FPN1、hepcidin等蛋白表达的调控及其机制研究的最新进展。
