Extensive iron deposition has been observed in the midbrain substantia nigra （SN） of Parkinson＇s disease （PD） patients, but the mechanisms of iron deposition in the SN remain poorly understood. The present study ...Extensive iron deposition has been observed in the midbrain substantia nigra （SN） of Parkinson＇s disease （PD） patients, but the mechanisms of iron deposition in the SN remain poorly understood. The present study investigated the relationship between dopaminergic neuronal damage, iron content changes, and divalent metal transporter 1 （DMT1） in the midbrain SN of PD rats to explore the relationship between time of iron deposition and DMT1 expression. Frozen midbrain SN sections from model rats were stained with Perls＇ iron. Results showed massive loss of tyrosine hydroxylase （TH）-positive cells in the SN and increased DMT1 expression in model group rats. No obvious iron deposition was observed in the SN during early stages after damage, but significant iron deposition was detected at 8 weeks post-injury. Results demonstrate that the loss of TH-positive cells in the SN appeared simultaneously with increased DMT1 expression. Extensive iron deposition occurred at 8 weeks post injury, which could be regarded as an early time window of iron deposition.展开更多
Iron plays a key role in Parkinson＇s disease （PD）. Increased iron content of the substantia nigra （SN） has been found in PD patients, and divalent metal transporter 1 （DMT1） has been shown to be up-regulated in...Iron plays a key role in Parkinson＇s disease （PD）. Increased iron content of the substantia nigra （SN） has been found in PD patients, and divalent metal transporter 1 （DMT1） has been shown to be up-regulated in the SN of both MPTP-induced PD models and PD patients. However, the mechanisms underlying DMT1 up-regulation are largely unknown. In the present study, we observed that in the SN of 6-hydroxydopamine （6-OHDA）-induced PD rats, DMT1 with the iron responsive element （IRE, DMTI＋IRE）, but not DMT1 without IRE （DMTI-IRE）, was up- regulated, suggesting that increased DMTI＋IRE expression might account for nigral iron accumulation in PD rats. This possibility was further assessed in an in vitro study using 6-OHDA-treated and DMTl＋IRE-over-expressing MES23.5 cells. In 6-OHDA-treated MES23.5 cells, increased iron regulatory protein （IRP） 1 and IRP2 expression was observed, while silencing of IRPs dramatically diminished 6-OHDA-indueed DMTI＋IRE up-regulation. Pre- treatment with N-acetyl-L-cysteine fully suppressed IRPs up-regulation by inhibition of 6-OHDA-indueed oxidative stress. Increased DMTI＋IRE expression resulted in increased iron influx by MES23.5 cells. Our data provide direct evidence that DMTI＋IRE up-regulation can account for IRE/IRP-dependent 6-OHDA-induced iron accumulation initiated by 6-OHDA-induced intracellular oxidative stress and that increased levels of intracellular iron result in ag- gravated oxidative stress. The results of this study provide novel evidence supporting the use of anti-oxidants in the treatment of PD, with the goal of inhibiting iron accumulation by regulation of DMT1 expression.展开更多
目的:研究运动性低血色素大鼠小肠铁吸收蛋白二价金属离子转运体1(divalent metal transporter1,DMT1)和膜铁转运蛋白1(ferroportin1,FPN1)表达的变化,探讨运动性低血色素的发生机制。方法:12只雄性Wistar大鼠随机分为对照组(CG)和实验...目的:研究运动性低血色素大鼠小肠铁吸收蛋白二价金属离子转运体1(divalent metal transporter1,DMT1)和膜铁转运蛋白1(ferroportin1,FPN1)表达的变化,探讨运动性低血色素的发生机制。方法:12只雄性Wistar大鼠随机分为对照组(CG)和实验组(EG)。实验组进行5周跑台训练,建立运动性低血色素模型。5周递增负荷跑台运动后,检测两组大鼠血常规和血清铁,采用Western Blot检测小肠上皮细胞DMT1和FPN1表达。结果:(1)实验组Hb显著低于对照组(P<0.01),运动性低血色素造模成功。(2)实验组大鼠小肠上皮细胞DMT1表达比对照组显著降低(P<0.05),FPN1表达比对照组显著下降(P<0.01)。(3)实验组血清铁和转铁蛋白饱合度显著低于对照组(P<0.05,P<0.01)。结论:长时间大强度运动会减少机体肠铁吸收,降低机体运铁能力,是引发运动性低血色素的原因之一。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
The amyloid beta precursor protein (APP) and its pathogenic byproduct β-amyloid peptide (Aβ) play central roles in the pathogenesis of Alzheimer’s disease (AD). Reduction in
基金the Scientific Research Common Program of Beijing Municipal Commission of Education,No.KM200610025008
文摘Extensive iron deposition has been observed in the midbrain substantia nigra （SN） of Parkinson＇s disease （PD） patients, but the mechanisms of iron deposition in the SN remain poorly understood. The present study investigated the relationship between dopaminergic neuronal damage, iron content changes, and divalent metal transporter 1 （DMT1） in the midbrain SN of PD rats to explore the relationship between time of iron deposition and DMT1 expression. Frozen midbrain SN sections from model rats were stained with Perls＇ iron. Results showed massive loss of tyrosine hydroxylase （TH）-positive cells in the SN and increased DMT1 expression in model group rats. No obvious iron deposition was observed in the SN during early stages after damage, but significant iron deposition was detected at 8 weeks post-injury. Results demonstrate that the loss of TH-positive cells in the SN appeared simultaneously with increased DMT1 expression. Extensive iron deposition occurred at 8 weeks post injury, which could be regarded as an early time window of iron deposition.
基金We thank Dr Wei-dong Le for providing the MES23.5 cell line. This work was supported by grants from the National Program of Basic Research sponsored by the Ministry of Science and Tech- nology of China （2006CB500704）, the National Natural Science Foundation of China （30930036, 30770757, 30870858） and the Natural Science Fund of Shandong Province for Distinguished Young Scholars （JQ200807）.
文摘Iron plays a key role in Parkinson＇s disease （PD）. Increased iron content of the substantia nigra （SN） has been found in PD patients, and divalent metal transporter 1 （DMT1） has been shown to be up-regulated in the SN of both MPTP-induced PD models and PD patients. However, the mechanisms underlying DMT1 up-regulation are largely unknown. In the present study, we observed that in the SN of 6-hydroxydopamine （6-OHDA）-induced PD rats, DMT1 with the iron responsive element （IRE, DMTI＋IRE）, but not DMT1 without IRE （DMTI-IRE）, was up- regulated, suggesting that increased DMTI＋IRE expression might account for nigral iron accumulation in PD rats. This possibility was further assessed in an in vitro study using 6-OHDA-treated and DMTl＋IRE-over-expressing MES23.5 cells. In 6-OHDA-treated MES23.5 cells, increased iron regulatory protein （IRP） 1 and IRP2 expression was observed, while silencing of IRPs dramatically diminished 6-OHDA-indueed DMTI＋IRE up-regulation. Pre- treatment with N-acetyl-L-cysteine fully suppressed IRPs up-regulation by inhibition of 6-OHDA-indueed oxidative stress. Increased DMTI＋IRE expression resulted in increased iron influx by MES23.5 cells. Our data provide direct evidence that DMTI＋IRE up-regulation can account for IRE/IRP-dependent 6-OHDA-induced iron accumulation initiated by 6-OHDA-induced intracellular oxidative stress and that increased levels of intracellular iron result in ag- gravated oxidative stress. The results of this study provide novel evidence supporting the use of anti-oxidants in the treatment of PD, with the goal of inhibiting iron accumulation by regulation of DMT1 expression.
基金Supported by"2009 Clinical and Basic Clinical Research Contest"of the Bureau for Clinical Research Support from the University of Chile Clinical Hospital
文摘AIM: To describe the variation that divalent metal transporter 1 (DMT1) shows in patients after Roux-en-Y gastric bypass (RYGB) surgery.
基金This work was supported by the National Natural Science Foundation of China (No. 30271441) Key Project of Shandong Educational Committee (J01 K03) and Qingdao Municipal Science & Technology Commission (02-1-KJ-YJ-49).
文摘目的:研究运动性低血色素大鼠小肠铁吸收蛋白二价金属离子转运体1(divalent metal transporter1,DMT1)和膜铁转运蛋白1(ferroportin1,FPN1)表达的变化,探讨运动性低血色素的发生机制。方法:12只雄性Wistar大鼠随机分为对照组(CG)和实验组(EG)。实验组进行5周跑台训练,建立运动性低血色素模型。5周递增负荷跑台运动后,检测两组大鼠血常规和血清铁,采用Western Blot检测小肠上皮细胞DMT1和FPN1表达。结果:(1)实验组Hb显著低于对照组(P<0.01),运动性低血色素造模成功。(2)实验组大鼠小肠上皮细胞DMT1表达比对照组显著降低(P<0.05),FPN1表达比对照组显著下降(P<0.01)。(3)实验组血清铁和转铁蛋白饱合度显著低于对照组(P<0.05,P<0.01)。结论:长时间大强度运动会减少机体肠铁吸收,降低机体运铁能力,是引发运动性低血色素的原因之一。
文摘The amyloid beta precursor protein (APP) and its pathogenic byproduct β-amyloid peptide (Aβ) play central roles in the pathogenesis of Alzheimer’s disease (AD). Reduction in
