目的探讨银杏叶提取物对帕金森患者血清黑质二价金属离子转运蛋白(divalent metal transporter1,DMT1)、葡萄糖调节蛋白75(glucose regulated protein 75,grp75)及神经功能的影响。方法帕金森患者38例,根据用药不同分为对照组和实验组,...目的探讨银杏叶提取物对帕金森患者血清黑质二价金属离子转运蛋白(divalent metal transporter1,DMT1)、葡萄糖调节蛋白75(glucose regulated protein 75,grp75)及神经功能的影响。方法帕金森患者38例,根据用药不同分为对照组和实验组,每组各19例,对照组患者给予多巴丝肼片,实验组在对照组的基础上给予银杏叶提取物片,治疗连续4周。治疗结束后,对所有患者黑质DMT1、grp75及认知功能进行检测。结果与治疗前相比,治疗后2组患者的黑质DMT1水平较低(P<0.05);与对照组相比,实验组患者治疗后黑质DMT1水平较低(P<0.05)。与治疗前相比,治疗后2组患者的grp75水平较高(P<0.05),与对照组相比,实验组患者治疗后grp75水平较高(P<0.05)。与治疗前相比,治疗后2组患者的Mo CA评分较高(P<0.05),HAMD评分较低(P<0.05);与对照组相比,实验组患者治疗后Mo CA评分较高(P<0.05),HAMD评分较低(P<0.05)。结论银杏叶提取物能够显著降低帕金森患者黑质DMT1水平,升高grp75水平,改善认知功能。展开更多
从分子结构与分布、生理功能及其对二价金属离子吸收的调控机制等方面对二价金属离子转运蛋白1(divalent metal transporter 1,DMT1)的国内外研究现状进行了综述。旨在通过对DMT1在微量元素吸收中的作用机制的研究,来提高动物微量元素...从分子结构与分布、生理功能及其对二价金属离子吸收的调控机制等方面对二价金属离子转运蛋白1(divalent metal transporter 1,DMT1)的国内外研究现状进行了综述。旨在通过对DMT1在微量元素吸收中的作用机制的研究,来提高动物微量元素的吸收效率和利用率。展开更多
铁是生物体最丰富的微量金属元素之一,小肠是机体铁吸收和铁稳态调节最关键结构,小肠吸收细胞对非血红素铁的吸收摄取主要由二价金属离子转运体(divalent metal transporter1,DMT1)介导的。DMT1对铁的吸收转运主要通过囊泡运输和载体运...铁是生物体最丰富的微量金属元素之一,小肠是机体铁吸收和铁稳态调节最关键结构,小肠吸收细胞对非血红素铁的吸收摄取主要由二价金属离子转运体(divalent metal transporter1,DMT1)介导的。DMT1对铁的吸收转运主要通过囊泡运输和载体运输实现的。囊泡运输主要包括DMT1形成吸收铁的囊泡、与apo-Tf囊泡融合、分离、分选转运完成的;载体运输则是在肠表面H+电化学梯度的驱动下将铁转入细胞内的。本文着重介绍了最近国内外关于DMT1在小肠非血红素铁吸收转运中的作用机制的最新研究进展。展开更多
二价金属离子转运蛋白1(divalent metal transporter 1,DMT1)是一种在哺乳动物广泛表达的金属离子转运载体,参与机体内多种金属离子的转运。本文综述DMT1分子结构与分布、生理功能及其对二价金属离子吸收的调控机制,旨在通过对DMT1在微...二价金属离子转运蛋白1(divalent metal transporter 1,DMT1)是一种在哺乳动物广泛表达的金属离子转运载体,参与机体内多种金属离子的转运。本文综述DMT1分子结构与分布、生理功能及其对二价金属离子吸收的调控机制,旨在通过对DMT1在微量元素吸收中的作用机制的研究,来提高动物微量元素的吸收效率和利用率。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
Objective To investigate the potential involvement of DMT1(IRE) protein in the brain vascular system in vivo during Pb exposure. Methods Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, a...Objective To investigate the potential involvement of DMT1(IRE) protein in the brain vascular system in vivo during Pb exposure. Methods Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the m RNA. Results Pb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1(IRE) protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1(IRE) m RNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1(IRE). Conclusion These results suggest that Pb is transported into the brain through DMT1(IRE), and the ERK MAPK pathway is involved in DMT1(IRE)-mediated transport regulation in brain vascular system in vivo.展开更多
This study aims to reveal the role of metal ion transporter DMT1 in neurotoxicity induced by Aβ142 oligomers.We exposed SH-SY5Y cells(S-DMT1)stably overexpressing the DMT1 gene and SH-SY5Y cells(SGFP)overexpressing e...This study aims to reveal the role of metal ion transporter DMT1 in neurotoxicity induced by Aβ142 oligomers.We exposed SH-SY5Y cells(S-DMT1)stably overexpressing the DMT1 gene and SH-SY5Y cells(SGFP)overexpressing empty green fluorescent protein to AB.42 oligomers.CCK8 and Hoechst 33258 were used to detect the cell death rate and apoptotic rate.W estern blotting was used to detect the levels of apoptotic proteins caspase-3,Bax and Bcl-2.The results of CCK8 experiments showed that compared with SGFP cells,the number of viable cells in S-DMT1 cells after Aβ42 oligomer treatment was significantly reduced.Heochst33258 staining results showed that the rate of nuclear shrinkage in S-DMT1 cells treated with Aβ142 oligomer was significantly higher than that in SGFP group.Moreover,the levels of caspase-3 and Bax proteins in S-DMT1 cells were higher than those in SGFP group,while BcI-2 decreased after Aβ42 oligomers.DMT1 overexpression increases the toxic effects of Aβ42 oligomers by promoting apoptosis.4.Regulation of"P35/P25-CDK5-Tau"signaling pathway in hippocampi and prefrontal cortex of AD rats by electroacupuncture.展开更多
Background and aims: While upregulation of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (IREG1)within duodenal enterocytes is reported in patients with hereditary haemochromatosis (HH), these findings...Background and aims: While upregulation of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (IREG1)within duodenal enterocytes is reported in patients with hereditary haemochromatosis (HH), these findings are controversial. Furthermore,the effect of HFE, the gene mutated in HH, on expression of these molecules is unclear. This study examines duodenal expression of these three molecules in HH patients(prior to and following phlebotomy), in patients with iron deficiency (ID), and in controls. Methods: DMT1, IREG1, and HFE mRNA were measured in duodenal tissue of C282Y homozygous HH patients, in ID patients negative for the C282Y mutation with a serum ferritin concentration less than 20 μ g/l,and in controls negative for C282Y and H63D mutations with normal iron indices, using real time polymerase chain reaction.Resells: DMT1 and IREG1 mRNA levels were not significantly different in non-phlebotomised (untreated) HH patients compared with controls. DMT1 expression was significantly increased in HH patients who had undergone phlebotomy therapy(treated) and in patients with ID compared with controls.IREG1 was significantly increased in ID patients relative to controls, and while IREG1 expression was 1.8-fold greater in treated HH patients, this was not statistically significant.HFE mRNA expression was not significantly different in any of the groups investigated relative to controls. Conclusions:These findings demonstrate that untreated HH patients do not have increased duodenal DMT1 and IREG mRNA, but rather phlebotomy increases expression of these molecules, reflecting the effect of phlebotomy induced erythropoiesis. Finally, HFE appears to play a minor role in the regulation of iron absorption by the duodenal enterocyte.展开更多
文摘目的探讨银杏叶提取物对帕金森患者血清黑质二价金属离子转运蛋白(divalent metal transporter1,DMT1)、葡萄糖调节蛋白75(glucose regulated protein 75,grp75)及神经功能的影响。方法帕金森患者38例,根据用药不同分为对照组和实验组,每组各19例,对照组患者给予多巴丝肼片,实验组在对照组的基础上给予银杏叶提取物片,治疗连续4周。治疗结束后,对所有患者黑质DMT1、grp75及认知功能进行检测。结果与治疗前相比,治疗后2组患者的黑质DMT1水平较低(P<0.05);与对照组相比,实验组患者治疗后黑质DMT1水平较低(P<0.05)。与治疗前相比,治疗后2组患者的grp75水平较高(P<0.05),与对照组相比,实验组患者治疗后grp75水平较高(P<0.05)。与治疗前相比,治疗后2组患者的Mo CA评分较高(P<0.05),HAMD评分较低(P<0.05);与对照组相比,实验组患者治疗后Mo CA评分较高(P<0.05),HAMD评分较低(P<0.05)。结论银杏叶提取物能够显著降低帕金森患者黑质DMT1水平,升高grp75水平,改善认知功能。
文摘铁是生物体最丰富的微量金属元素之一,小肠是机体铁吸收和铁稳态调节最关键结构,小肠吸收细胞对非血红素铁的吸收摄取主要由二价金属离子转运体(divalent metal transporter1,DMT1)介导的。DMT1对铁的吸收转运主要通过囊泡运输和载体运输实现的。囊泡运输主要包括DMT1形成吸收铁的囊泡、与apo-Tf囊泡融合、分离、分选转运完成的;载体运输则是在肠表面H+电化学梯度的驱动下将铁转入细胞内的。本文着重介绍了最近国内外关于DMT1在小肠非血红素铁吸收转运中的作用机制的最新研究进展。
文摘二价金属离子转运蛋白1(divalent metal transporter 1,DMT1)是一种在哺乳动物广泛表达的金属离子转运载体,参与机体内多种金属离子的转运。本文综述DMT1分子结构与分布、生理功能及其对二价金属离子吸收的调控机制,旨在通过对DMT1在微量元素吸收中的作用机制的研究,来提高动物微量元素的吸收效率和利用率。
基金supported by National Natural Science Foundation of China(No.81472478)Medical Science Youth Breeding Project of PLA(13QNP161)
文摘Objective To investigate the potential involvement of DMT1(IRE) protein in the brain vascular system in vivo during Pb exposure. Methods Three groups of male Sprague-Dawley rats were exposed to Pb in drinking water, among which two groups were concurrently administered by oral gavage once every other day as the low and high Fe treatment group, respectively, for 6 weeks. At the same time, the group only supplied with high Fe was also set as a reference. The animals were decapitated, then brain capillary-rich fraction was isolate from cerebral cortex. Western blot method was used to identify protein expression, and RT-PCR to detect the change of the m RNA. Results Pb exposure significantly increased Pb concentrations in cerebral cortex. Low Fe dose significantly reduced the cortex Pb levels, However, high Fe dose increased the cortex Pb levels. Interestingly, changes of DMT1(IRE) protein in brain capillary-rich fraction were highly related to the Pb level, but those of DMT1(IRE) m RNA were not significantly different. Moreover, the consistent changes in the levels of p-ERK1/2 or IRP1 with the changes in the levels of DMT1(IRE). Conclusion These results suggest that Pb is transported into the brain through DMT1(IRE), and the ERK MAPK pathway is involved in DMT1(IRE)-mediated transport regulation in brain vascular system in vivo.
文摘目的进一步确定二价金属离子转运体1(DMT1)在人胎盘绒毛膜癌细胞(Be Wo)中的表达定位,以及缺铁状态下m RNA的表达变化。方法采用免疫细胞化学技术观察DMT1在Be Wo细胞中的表达定位,采用实时荧光定量聚合酶链反应检测DMT1在Be Wo细胞缺铁状态下m RNA的表达变化。结果 DMT1在Be Wo细胞中呈阳性表达,其弥漫性表达定位于细胞质和细胞膜上;DMT1+IRE m RNA和DMT1-IRE m RNA的相对表达量随缺铁干预浓度和时间的增加而上调。DMT1+IRE m RNA的相对表达量高于DMT1-IRE m RNA。结论DMT1大量表达在Be Wo细胞质和细胞膜上,且表达受机体不同铁水平的调节,说明其在胎盘铁转运过程中发挥重要作用,为进一步探讨胎盘铁转运分子机制提供实验基础。
文摘This study aims to reveal the role of metal ion transporter DMT1 in neurotoxicity induced by Aβ142 oligomers.We exposed SH-SY5Y cells(S-DMT1)stably overexpressing the DMT1 gene and SH-SY5Y cells(SGFP)overexpressing empty green fluorescent protein to AB.42 oligomers.CCK8 and Hoechst 33258 were used to detect the cell death rate and apoptotic rate.W estern blotting was used to detect the levels of apoptotic proteins caspase-3,Bax and Bcl-2.The results of CCK8 experiments showed that compared with SGFP cells,the number of viable cells in S-DMT1 cells after Aβ42 oligomer treatment was significantly reduced.Heochst33258 staining results showed that the rate of nuclear shrinkage in S-DMT1 cells treated with Aβ142 oligomer was significantly higher than that in SGFP group.Moreover,the levels of caspase-3 and Bax proteins in S-DMT1 cells were higher than those in SGFP group,while BcI-2 decreased after Aβ42 oligomers.DMT1 overexpression increases the toxic effects of Aβ42 oligomers by promoting apoptosis.4.Regulation of"P35/P25-CDK5-Tau"signaling pathway in hippocampi and prefrontal cortex of AD rats by electroacupuncture.
文摘Background and aims: While upregulation of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (IREG1)within duodenal enterocytes is reported in patients with hereditary haemochromatosis (HH), these findings are controversial. Furthermore,the effect of HFE, the gene mutated in HH, on expression of these molecules is unclear. This study examines duodenal expression of these three molecules in HH patients(prior to and following phlebotomy), in patients with iron deficiency (ID), and in controls. Methods: DMT1, IREG1, and HFE mRNA were measured in duodenal tissue of C282Y homozygous HH patients, in ID patients negative for the C282Y mutation with a serum ferritin concentration less than 20 μ g/l,and in controls negative for C282Y and H63D mutations with normal iron indices, using real time polymerase chain reaction.Resells: DMT1 and IREG1 mRNA levels were not significantly different in non-phlebotomised (untreated) HH patients compared with controls. DMT1 expression was significantly increased in HH patients who had undergone phlebotomy therapy(treated) and in patients with ID compared with controls.IREG1 was significantly increased in ID patients relative to controls, and while IREG1 expression was 1.8-fold greater in treated HH patients, this was not statistically significant.HFE mRNA expression was not significantly different in any of the groups investigated relative to controls. Conclusions:These findings demonstrate that untreated HH patients do not have increased duodenal DMT1 and IREG mRNA, but rather phlebotomy increases expression of these molecules, reflecting the effect of phlebotomy induced erythropoiesis. Finally, HFE appears to play a minor role in the regulation of iron absorption by the duodenal enterocyte.
