鹿茸多肽对缺铁性贫血大鼠的治疗作用及机制研究

摘要 目的：研究鹿茸多肽（PAP）对缺铁性贫血（IDA）大鼠的治疗作用并探讨其可能机制。方法：使用缺铁饲料诱导IDA大鼠模型,将40只IDA大鼠随机分为模型组（灌胃等体积的生理盐水）,Low-PAP组、Medium-PAP组和High-PAP组（分别灌胃30、60和120 mg/kg的PAP）,每组10只,另选取10只正常饲料喂养的同龄健康大鼠作为对照组（灌胃等体积的生理盐水）。每天灌胃1次,疗程为4周。末次给药24 h后,测量各组大鼠的体重、肝脏和脾脏指数,对肝脏和脾脏组织进行苏木素伊红（HE）染色。通过ELISA法检测血红蛋白（Hb）和促红细胞生成素（EPO）含量,通过比色法检测血清铁（SI）含量,通过透射电子显微镜观察肝脏和脾脏线粒体超微结构。使用相应试剂盒检测血清氧化应激指标水平。通过Western blot检测骨髓转铁蛋白受体（TFR）蛋白表达水平。结果：与模型组相比,Low-PAP组、Medium-PAP组和High-PAP组大鼠体重均升高,肝脏和脾脏指数均降低（P<0.05）,且大鼠的肝脏和脾脏形态和线粒体超微结构明显改善,Hb、EPO和SI水平均升高（P<0.05）。与模型组相比,Low-PAP组、Medium-PAP组和High-PAP组大鼠的血清超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-PX）水平均升高,而丙二醛（MDA）降低（P<0.05）。与模型组相比,Low-PAP组、Medium-PAP组和High-PAP组大鼠的骨髓TFR蛋白相对表达量降低（P<0.05）。结论：本研究表明PAP可有效减轻IDA大鼠的临床症状,促进红细胞生成,增强造血功能,改善铁代谢,提高抗氧化能力,促进线粒体合成。     

川芎定痛颗粒对硝酸甘油致偏头痛大鼠作用的研究

目的观察川芎定痛颗粒对硝酸甘油致偏头痛大鼠的作用。方法将60只SD大鼠随机分为正常对照组、模型组、佐米曲普坦组(0.83 mg每千克体质量)、川芎定痛颗粒高剂量组(1.75 g浸膏粉每千克体质量)、中剂量组(0.88 g浸膏粉每千克体质量)、低剂量组(0.44 g浸膏粉每千克体质量)6组,灌胃给予相应药物5 d后,除正常对照组外,对大鼠皮下注射硝酸甘油每千克体质量10 mg,建立偏头痛大鼠模型,通过ELASA方法检测大鼠血浆中5-羟色胺(5-HT)、内皮素(ET)、去甲肾上腺素(NE)和脑组织中5-HT、多巴胺(DA)、NE的含量。结果与正常对照组比较,模型组血浆中5-HT与ET含量明显降低,差异有统计学意义(P0.05),川芎定痛颗粒高、中剂量组可明显升高其含量,与模型组比较差异有统计学意义(P0.05),佐米曲普坦组、川芎定痛颗粒低剂量组有升高的趋势;NE含量明显降低,正常对照组与模型组比较差异有统计学意义(P0.05),川芎定痛颗粒高剂量组可明显升高其含量,而佐米曲普坦组、川芎定痛颗粒中、低剂量组则是含量降低,与模型组比较差异均有统计学意义(P0.05)。与正常对照组比较,模型组脑组织内5-HT含量差异虽无统计学意义,但降低趋势明显,且川芎定痛颗粒高剂量组能明显升高其含量,与模型组比较有统计学意义(P0.05),佐米曲普坦组、中、低剂量亦有升高的趋势;与正常对照组比较,模型组脑组织内NE含量明显升高,有统计学差异(P0.05),川芎定痛颗粒高、中剂量组能明显降低其含量,与模型组比较有统计学差异(P0.05);与正常对照组比较,模型组脑组织中DA含量降低,有统计学差异(P0.05),川芎定痛颗粒高、中剂量组能升高其含量,具有统计学意义(P0.05)。结论川芎定痛颗粒对硝酸甘油致偏头痛大鼠有治疗作用,其机制可能与调节模型大鼠血浆及脑组织内单胺类神经递质5-HT、NE、ET、DA含量有关。     

地榆皂苷类成分对环磷酰胺致小鼠骨髓抑制的保护作用研究

为了观察地榆皂苷类成分对骨髓抑制的保护作用,本文采用腹腔注射环磷酰胺致小鼠骨髓抑制模型。造模成功后,将骨髓抑制小鼠按体重随机分为:模型对照组、集落刺激因子组、地榆皂苷Ⅰ5、2.5、0.5 mg/kg三个剂量组,地榆皂苷Ⅱ5、2.5、0.5 mg/kg三个剂量组,地榆皂苷元5、2.5、0.5 mg/kg三个剂量组,另设正常对照组。连续灌胃7 d,每天一次,以外周血液白细胞数量、骨髓细胞DNA含量和CD34+的表达以及骨髓细胞O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)蛋白的表达为评价指标,研究地榆皂苷类成分对CTX所致骨髓抑制的治疗作用。结果显示地榆皂苷类成分可显著升高小鼠WBC(P0.05);显著升高小鼠骨髓DNA含量(P0.05);显著促进CD34+的表达(P0.05);显著促进MGMT蛋白的表达(P0.05)。通过本研究可以看出地榆皂苷类成分可显著拮抗CTX所致小鼠骨髓抑制。     

低频交变磁场刺激对缺铁性贫血大鼠贫血改善的作用研究

目的:明确低频正弦波交变电磁场对缺铁性贫血大鼠贫血改善的作用效果,为其未来的临床应用提供实验依据。方法:雄性断乳的SPF级Sprague-Dawley(SD)大鼠,共36只,随机的等分为空白对照组(n=12)、缺铁性贫血组(n=12)和缺铁性贫血+电磁场刺激组(n=12)。缺铁性贫血组和缺铁性贫血+电磁场刺激组的大鼠饲养以低铁饲料和去离子水,每周尾静脉放血1 m L。空白对照组大鼠饲养以常规饲料和普通蒸馏水,且不予尾静脉放血。对缺铁性贫血+电磁场刺激组的12只大鼠施加全身低频交变电磁场刺激,每天刺激2小时,连续刺激10周。实验结束后提取大鼠血液样本,使用氰化高铁血红蛋白法进行测定全血血红蛋白含量,使用专用试剂盒测定血清铁和总铁结合力;提取肝脏和脾脏组织,对肝脏铁和脾脏铁含量进行测定。结果:全身暴露低频交变电磁场刺激显著提高了缺铁性贫血大鼠体重(P0.05),提升了其血清铁含量(P0.05),显著提高全血血红蛋白含量(P0.05),并显著降低了缺铁性贫血大鼠血清总铁结合力(P0.05);同时,电磁刺激也显著提高了缺铁性贫血大鼠肝脏铁和脾脏铁含量(P0.05)。结论:交变电磁场作为一种经济、安全、无创的物理作用方式,具有较为显著的缺铁性贫血的改善效果。     

铁过载人群外周血相关指标变化分析

目的：探讨铁过载人群外周血相关指标的变化及血清铁蛋白(SF)和铁营养、血常规指标之间的关系,为铁过载的诊断及分类提供科学依据。方法：随机抽取196名铁正常人群(男SF:15~200μg/L、女SF：15~150μg/L)和226名铁过载人群(男SF:＞200μg/L、女SF:＞150μg/L)。采用放射免疫法检测SF浓度,检测铁营养状况和血常规指标,分析血清铁蛋白和铁营养、血常规指标之间的相关性。结果：铁过载人群血清铁浓度22.93μmol/L和转铁蛋白饱和度36%显著高于铁正常组的17.83μmol/L和28%(P<0.05),铁过载组人群不饱和铁结合力水平为40.69μmol/L和转铁蛋白浓度245.67mg/dL,显著低于正常组的46.97μmol/L和264.33 mg/dL(P<0.05),两组间总铁结合力水平的比较无显著差异(P>0.05);铁过载组红细胞计数平均为4.98×1012/L和血红蛋白含量平均为155g/L,显著高于铁正常组的4.82×1012/L和147g/L (P<0.05),铁过载组红细胞压积44%和平均红细胞血红蛋白含量31.17pg,显著高于铁正常组人群的42%和30.61pg (P<0.05),两组之间白细胞计数和血小板计数的比较无显著差异(P>0.05)。相关分析显示,血清铁蛋白与血清铁、转铁蛋白饱和度、红细胞计数、白细胞计数、血红蛋白、红细胞压积和平均红细胞血红蛋白含量呈显著正相关(P<0.05),与不饱和铁结合力、转铁蛋白水平和血小板计数呈显著负相关(P<0.05)。结论：中老年人群铁过载时,机体内血清铁、转铁蛋白饱和度、红细胞计数、血红蛋白、红细胞压积和平均红细胞血红蛋白含量均升高,不饱和铁结合力和转铁蛋白水平均降低;血清铁蛋白和血红蛋白呈显著正相关。因此,采用血常规检查和铁营养指标的联合检测来评价铁过载的程度,可为铁过载的早期发现、早期治疗提供科学依据。     

百合知母汤对哮喘大鼠血清、肺泡灌洗液中SP-A 及脏器系数变化的影响

目的:通过百合知母汤对哮喘大鼠的干预,探讨该治疗方法的作用机理。方法:将大鼠随机分成正常组、哮喘模型组、中药大、中、小剂量组、地米组、中西药联用组,除正常组外经卵蛋白免疫建立模型,ELISA法检测各组血清和BALF中SP-A的含量;计算肺脏、胸腺和脾脏的脏器系数。结果:与正常组相比,模型组及小剂量组血清、BALF中SP-A明显降低(P<0.05);与模型组比较,中药各剂量组、地米组及中西药联用组血清和BALF中SP-A有统计学意义(P<0.05);中药各剂量组间比较,中剂量组血清和BALF中SP-A均高于小剂量组,差异有统计学意(P<0.05);模型组肺脏器系数明显高于正常对照组(P<0.05)。结论:百合知母汤可显著升高血清和BALF中SP-A含量,对肺组织有很大影响。     

地榆鞣质对环磷酰胺致小鼠骨髓抑制的保护作用研究

为了观察地榆鞣质对骨髓抑制的保护作用,本文采用腹腔注射环磷酰胺致小鼠骨髓抑制模型。造模成功后,将骨髓抑制小鼠按体重随机分为:模型组、集落刺激因子组、地榆鞣质20、10、5 mg/kg三个剂量组,另设正常对照组。连续灌胃10 d,每天一次,以外周血液白细胞数量、骨髓细胞DNA含量和CD34+的表达以及骨髓细胞O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)蛋白的表达为评价指标,研究地榆鞣质对CTX所致骨髓抑制的治疗作用。结果显示地榆鞣质可显著升高小鼠外周血WBC(P0.05);显著升高小鼠骨髓DNA含量(P0.05);显著促进CD34+的表达(P0.05);显著促进MGMT蛋白的表达(P0.05)。通过本研究可以看出地榆鞣质可显著拮抗CTX所致小鼠骨髓抑制。     

BN大鼠和豚鼠对卵清白蛋白致主动过敏反应的免疫学特性比较

目的 比较BN大鼠和豚鼠对卵清白蛋白(OVA)致敏前后机体免疫学特性的变化.方法 BN大鼠和豚鼠分别用OVA(每只1 mg)隔日致敏(i.p.),共5次;于末次致敏第10天以OVA(每只2 mg)激发致敏(i.v.);分别设正常对照组和OVA致敏组.于激发致敏后1h处死动物,分离腹腔肥大细胞、脾脏和骨髓,并制备脾脏和骨髓淋巴细胞.以annexin-V作为标志检测肥大细胞活性,同时以Fluo-3/AM标记胞内钙离子,检测钙离子水平;以PHA和LPS作为有丝分裂原,分别检测脾脏和骨髓T、B淋巴细胞活性.结果 ①致敏BN大鼠和豚鼠脾脏及骨髓T、B淋巴细胞活性均升高,其中骨髓淋巴细胞活性BN大鼠显著高于豚鼠,脾脏淋巴细胞活性两种属间差异无显著性;②致敏后,腹腔肥大细胞活性两种属间差异无显著性,但BN大鼠致敏后是致敏前的6倍,豚鼠是3倍;③肥大细胞内钙离子水平两种属致敏后均升高,豚鼠致敏前后钙离子水平具有统计学意义.结论 OVA致敏后,BN大鼠骨髓淋巴细胞活性明显高于豚鼠,豚鼠肥大细胞内钙离子较BN大鼠升高明显,肥大细胞活性两者无明显差异.因此,在实验中可以根据两种属在过敏反应中的特点以及具体的实验要求选择动物模型.     

溶血致新生大鼠高胆红素血症动物模型的建立及评价

目的探讨建立操作简便可行、成功率高、具有良好模拟性的新生大鼠高胆红素血症动物型,为开展高胆红素血症致核黄疸及相关神经损伤机制研究提供实验基础模型。方法随机选取7日龄SD大鼠,分别采用25、50、75 mg/kg三个梯度腹腔内注射盐酸苯肼,建立溶血致高胆红素血症动物模型,同时设立对照组,分别在实验处理48h后,测定血、脑组织胆红素、同时进行脑组织NSE分析对模型进行评价。结果三组实验组分别与对照组相比,血、脑组织胆红素、脑组织NSE均大于对照组,差异具有显著性(P0.05),而血红蛋白含量小于对照组,差异具有显著性(P0.05);50 mg和75 mg剂量组血、脑组织胆红素、脑组织神经元特异性烯醇化酶(NSE)均大于25 mg剂量组,而血红蛋白含量小于25 mg剂量组,差异具有显著性(P0.05);50 mg和75 mg剂量组间相比各项指标差异无显著性(P0.05)。结论腹腔注射盐酸苯肼能够制作出符合临床特征的高胆红素动物模型,50 mg/kg为最佳浓度,是建立新生儿高胆红素血症动物模型的理想方法。     

黄连素对糖尿病大鼠胰岛素抵抗的治疗作用*

目的:探讨黄连素对链脲佐菌素所致糖尿病大鼠胰岛素抵抗的治疗作用。方法:采用链脲佐菌素腹腔注射的方式建立大鼠糖尿病模型,将实验大鼠分为5组:分别为模型组、黄连素低(100 mg/kg)、黄连素中(200 mg/kg)、黄连素高(300 mg/kg)剂量组和阳性对照组(二甲双胍:50 mg/kg),每组10只。另取10只正常大鼠作为正常组。黄连素低、中、高剂量组小鼠每天分别灌胃100、200和300 mg/kg黄连素;对照组每天灌胃二甲双胍50 mg/kg;正常组和模型组每天给予相同体积的生理盐水进行灌胃;1次/天,连续灌胃4周。通过测定大鼠血FBG、果糖胺水平,OGTT实验,胰岛素(FINS)水平,并计算大鼠胰岛素抵抗指数(HOMA-IR)来评价黄连素对糖尿病大鼠胰岛素抵抗作用。结果:与正常组相比,给药前模型组大鼠静脉血FBG含量显著升高(P＜0.05);与模型组比较,给药2周及以后给药4周后阳性对照组、黄连素中剂量组和高剂量组大鼠静脉血FBG含量均显著下降(P＜0.05);给药4周后,阳性对照组、黄连素低、中、高剂量组OGTT实验结果显示在不同时间节点的血糖值均显著低于模型组(P＜ 0.05),阳性对照组、黄连素低、中、高剂量组FBG、果糖胺水平和HOMA-IR指标均低于模型组(P＜0.05);而胰岛素水平水平较模型组显著升高(P＜0.05)。结论:黄连素可明显降低大鼠的空腹血糖、果糖胺含量,提高胰岛素含量,对链脲佐菌素所致糖尿病大鼠的胰岛素抵抗有明显治疗作用。且一定范围内,黄连素剂量越高,对糖尿病大鼠胰岛素抵抗作用越明显。     

Iron: Key player in cancer and cell cycle?

BackgroundIron is an essential element for growth and metabolic activities of all living organisms but remains in its oxyhydroxide ferric ion form in the surrounding. Unavailability of iron in soluble ferrous form led to development of specific pathways and machinery in different organisms to make it available for use and maintain its homeostasis. Iron homeostasis is essential as under different circumstances iron in excess as well as deprivation leads to different pathological conditions in human.ObjectiveThis review highlights the current findings related to iron excess as well as deprivation with regards to cellular proliferation.ConclusionsIron excess is extensively associated with different types of cancers viz. colorectal cancer, breast cancer etc. by producing an oxidative stressed condition and alteration of immune system. Ironically its deprivation also results in anaemic conditions and leads to cell cycle arrest at different phases with mechanism yet to be explored. Iron deprivation arrests cell cycle at G1/S and in some cases at G2/M checkpoints resulting in growth arrest. However, in some cases iron overload arrests cell cycle at G1 phase by blocking certain signalling pathways. Certain natural and synthetic iron chelators are being explored from few decades to combat diseases caused by alteration in iron homeostasis.     

鱼腥蓝细菌PCC7120铁吸收机制

铁离子是鱼腥蓝细菌PCC7120进行呼吸作用、光合作用和固氮作用中相关酶的重要辅基之一,缺铁将严重影响蓝细菌的生存.富氧的生态环境中铁通常以不溶的Fe3+形式存在,不易被细胞吸收利用.低铁条件下,鱼腥蓝细菌PCC7120分泌能螯合铁离子的嗜铁素,通过外膜上相应的转运体将嗜铁素-铁复合物转运到细胞内.综述了近年来在嗜铁素的种类及其生物合成途径、铁吸收系统的组成和功能等方面的最新进展,分析了铁吸收系统的调控机制,为进一步开展鱼腥蓝细菌铁吸收机制的研究提供依据.     

Siderophore Production and Iron Reduction by Pseudomonas mendocina in Response to Iron Deprivation

In aerobic environments microorganisms are faced with a discrepancy of ~10 orders of magnitude between the available Fe (~10^-17M) and their metabolic requirement for it (~10^-7M). In contrast to facultative anaerobic environments, where dissimilatory iron-reducing bacteria (DIRB) are often abundant, few studies have detailed microbial interactions with Fe(III) (hydr)oxides in aerobic environments. To better understand acquisition of Fe from Fe(III) (hydr)oxides, we investigated the production of siderophore and Fe(III) reduction by a strict aerobe in the presence of synthetic hematite as a source of Fe. Pseudomonas mendocina grew best when Fewas supplied as FeEDTA (~1.8x10⁸ colony-forming units [CFU] ml^-1), grew abundantly when Fe was supplied as hematite (~1.2x10⁸ CFU ml^-1), and grew poorly when Fe was withheld from the medium (~5.5x10⁷ CFU ml^-1). As expected, negligible siderophore was produced per cell when Fe was supplied as FeEDTA and more siderophore was produced in the hematite flasks than in the controls. Thus, growth of P. mendocina and the production of siderophore in the presence of hematite present compelling evidence that siderophore was produced as a mechanism to acquire Fe from hematite. For the Fe reduction experiments, Fe reduction by components of the supernatant fluid was induced weakly when Fe was supplied as hematite or as FeEDTA, but much more when the cells were cultured under extreme Fe deprivation. In fact, 16 times as much Fe reduction occurred in the controls as in the presence of either of the FeEDTA or hematite amendments. Our results, which contravene the long-held assumptions that Fe acquisition was facilitated solely by siderophores, provides a new perspective regarding microbial interactions with Fe bearing minerals.     

Differential effects of basolateral and apical iron supply on iron transport in Caco-2 cells

Iron homeostasis in the human body is maintained primarily through regulation of iron absorption in the duodenum. The liver peptide hepcidin plays a central role in this regulation. Additionally, expression and functional control of certain components of the cellular iron transport machinery can be influenced directly by the iron status of enterocytes. The significance of this modulation, relative to the effects of hepcidin, and the comparative effects of iron obtained directly from the diet and/or via the bloodstream are not clear. The studies described here were performed using Caco-2 cell monolayers as a model of intestinal epithelium, to compare the effects of iron supplied in physiologically relevant forms to either the apical or basolateral surfaces of the cells. Both sources of iron provoked increased cellular ferritin content, indicating iron uptake from both sides of the cells. Supply of basolateral transferrin-bound iron did not affect subsequent iron transport across the apical surface, but reduced iron transport across the basolateral membrane. In contrast, the apical iron supply led to subsequent reduction in iron transport across the apical cell membrane without altering iron export across the basolateral membrane. The apical and basolateral iron supplies also elicited distinct effects on the expression and subcellular distribution of iron transporters. These data suggest that, in addition to the effects of cellular iron status on the expression of iron transporter genes, different modes and direction of iron supply to enterocytes can elicit distinct functional effects on iron transport.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-015-0463-5) contains supplementary material, which is available to authorized users.     

细菌铁离子摄取系统与宿主免疫

铁是绝大多数细菌生存所必需的营养物质,参与了许多重要的生命过程。病原菌为了在宿主体内生长繁殖建立感染,进化出了多种从宿主体内摄取铁元素的机制。但过量的铁也会通过Fenton反应对细胞产生毒性,所以铁的摄取必须受到严格的调控。宿主为抵抗感染采取多种手段限制病原菌对于自身铁的利用,同时铁摄取系统也可以作为抗菌治疗的靶点。     

白念珠菌铁稳态调控网络研究进展

铁是绝大多数生物生长和代谢过程中必需的营养元素。尽管自然界中铁元素含量非常丰富,但是其生物可利用性却很低。作为一种人体常见的条件致病真菌,白念珠菌在漫长的进化过程中形成了复杂的铁稳态调控网络,能够应答环境中铁浓度的变化,增强菌株对环境的适应力。结合课题组研究工作,简要综述近几年关于铁代谢表达调控途径的研究进展,主要关注白念珠菌在环境铁匮乏条件下铁获得和调控策略,揭示白念珠菌体内铁离子摄取、转运、储存和利用机制。     

Elucidation of iron homeostasis in Acanthamoeba castellanii

Acanthamoeba castellanii is a ubiquitously distributed amoeba that can be found in soil, dust, natural and tap water, air conditioners, hospitals, contact lenses and other environments. It is an amphizoic organism that can cause granulomatous amoebic encephalitis, an infrequent fatal disease of the central nervous system, and amoebic keratitis, a severe corneal infection that can lead to blindness. These diseases are extremely hard to treat; therefore, a more comprehensive understanding of this pathogen’s metabolism is essential for revealing potential therapeutic targets. To propagate successfully in human tissues, the parasites must resist the iron depletion caused by nutritional immunity. The aim of our study is to elucidate the mechanisms underlying iron homeostasis in A. castellanii. Using a comparative whole-cell proteomic analysis of cells grown under different degrees of iron availability, we identified the primary proteins involved in Acanthamoeba iron acquisition. Our results suggest a two-step reductive mechanism of iron acquisition by a ferric reductase from the STEAP family and a divalent metal transporter from the NRAMP family. Both proteins are localized to the membranes of acidified digestive vacuoles where endocytosed medium and bacteria are trafficked. The expression levels of these proteins are significantly higher under iron-limited conditions, which allows Acanthamoeba to increase the efficiency of iron uptake despite the observed reduced pinocytosis rate. We propose that excessive iron gained while grown under iron-rich conditions is removed from the cytosol into the vacuoles by an iron transporter homologous to VIT/Ccc1 proteins. Additionally, we identified a novel protein that may participate in iron uptake regulation, the overexpression of which leads to increased iron acquisition.     

Transferrin and Iron Uptake by the Brain: Effects of Altered Iron Status

Transferrin (Tf) and iron uptake by the brain were measured in rats using 59Fe-125I-Tf and 131I-albumin (to correct for the plasma content of 59Fe and 125I-Tf in the organs). The rats were aged from 15 to 63 days and were fed (a) a low-iron diet (iron-deficient) or, as control, the same diet supplemented with iron, or (b) a chow diet with added carbonyl iron (iron overload), the chow diet alone acting as its control. Iron deficiency was associated with a significant decrease and iron overload with a significant increase in brain nonheme iron concentration relative to the controls. In each dietary treatment group, the uptake of Tf and iron by the brain decreased as the rats aged from 15 to 63 days. Both Tf and iron uptake were significantly greater in the iron-deficient rats than in their controls and lower in the iron-loaded rats than in the corresponding controls. Overall, iron deficiency produced about a doubling and iron overload a halving of the uptake values compared with the controls. In contrast to that in the brain, iron uptake by the femurs did not decrease with age and there was relatively little difference between the different dietary groups. 125I-Tf uptake by the brains of the iron-deficient rats increased very rapidly after injection of the labelled proteins, within 15 min reaching a plateau level which was maintained for at least 6 h. The uptake of 59Fe, however, increased rapidly for 1 h and then more slowly, and in terms of percentage of injected dose reached much higher values than did 125I-Tf uptake.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-dependent expression of hephaestin in the brain of ceruloplasmin-deficient mice

Aceruloplasminemia is an autosomal recessive disorder caused by mutations in the ceruloplasmin (CP) gene. It is characterized by iron accumulation in the brain and in visceral organs. However, little is known about the mechanism of iron transport in these regions. Adult CP null (CP^−/−) mice show increased iron deposition in several regions of brain, such as the cerebellum and brainstem. In this study, we investigated the expression of the ceruloplasmin homolog hephaestin (Heph) in the brain of CP^−/− mice as a function of age. In the cerebral cortex and caudate putamen of 80-week-old CP^−/− mice, the expression of Heph increased significantly whilst iron levels remain normal [Patel BN, Dunn RJ, Jeong SY, Zhu Q, Julien JP, David S. Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury. J Neurosci 2002;22(15):6578–6], indicating that Heph might compensate for the loss of CP. In contrast, the substantia nigra and cerebellum of 80-week-old CP^−/− mice accumulate iron but do not express high levels or significant decrease of Heph, suggesting that Heph does not replace CP in these regions. These data suggest that Heph may compensate for the loss of CP in a region-specific manner.