Iron deficiency down-regulates the Akt/TSC1-TSC2/mammalian Target of Rapamycin signaling pathway in rats and in COS-1 cells

Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity.     

黑蔓不同部位微量元素的测定

为了了解吉林省长白县山区所产卫矛科雷公藤属植物黑蔓的药理作用,扩大它的药用部位和应用范围,我们从无机元素与中药药效有密切关系的角度出发,实验测出黑蔓含有Ba、Si、Cu、Fe、Zn、Sn、Co、Mn、Mg、Ca、Se等无机元素,本文重点对其中人体必需的微量元素Cu、Fe、Zn、Se作了定量分析。     

催化分光光度法测定人发中微量铁

拟定了一简单实用的测定人发中铁的催化分光光度法。在实验条件下,人发中常见的数10种微量元素均不干扰铁的测定,回收率达86～106%。     

广西毛南族农村妇女铁营养状况调查

对450名广西环江县毛南族农村育龄妇女进行血清铁蛋白(SF)、红细胞游离原卟啉(FEP)及血红蛋白(Hb)3项铁指标测定.结果发现:铁缺乏症患病率为27.8%(其中ID4.2%,IDE 7.8%,IDA 15.8%).随着孕次或产次的增加,血红蛋白水平逐渐下降,铁缺乏症患病率逐渐增高.有妊娠或分娩史的妇女与未孕或未生育的妇女血红蛋白水平与铁缺乏症患病率比较均有显著性差异(P<0.05).     

Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson's disease: a LAMMA study

The Laser Microprobe Mass Analyzer (LAMMA) is a sensitive instrument for identifying and localizing trace elements in tissue samples. Using LAMMA, we have examined melanin-containing neurons of the substantia nigra in patients with Parkinson's disease (PD) and controls. We found that iron significantly accumulates within neuromelanin granules of patients with PD compared to controls. Increased aluminum was found in the neuromelanin granules of 2 of 3 PD cases but in no controls. The accumulation of iron and aluminum, which are known to promote oxidant stress, may account for the selective degeneration of neuromelanin-containing neurons in PD.     

锌铜镉铁与高血压病

用原子吸收光谙仪，测定２６例高血压病人血清和红细胞内锌、铜、镉、铁含量，并以３０名健康中年人作对照。结果发现：高血压病人红细胞内锌含量增加，血清铜、铁含量降低，血清及红细胞内镉元素均降低。各元素水平与血压读数间未发现相关性。     

Effects of training on iron status in cross-country skiers

Summary Haematological changes were studied in cross-country skiers during a 33-week training season (7 h a week). The daily amounts of training were calculated from the duration and the intensity of the exercise and then used to estimate training responses associated with a first order transfer function. The profile of system training responses (STR) was determined by convolution between the amounts of training and a first-order transfer function. Linear regressions were used to determine correlation coefficients between STR and iron status indices. Among the values for the time constants of decay, the one giving the best fit between STR and iron status indices was chosen. A relationship was noted between on the one hand STR and changes in serum ferritin concentration ([FERR]) and on the other hand STR and change in mean cell volume (MCV). The [FERR] was decreased and MCV was increased by training. It is suggested that a decrease in [FERR] could have been related to a decrease in total body iron stores. However, large and rapid changes in [FERR] could not have been a reflection of changes in total body iron stores. Equilibrium between [FERR] and total body iron stores could have been temporarily altered by the effects of training. Moreover, iron stores did not seem to have been sufficiently depleted to restrict erythropoiesis. The MCV increased slightly in response to intense training suggesting that training enhances the proportion of young erythrocytes.     

Distribution of ferritin in the rat hippocampus after kainate-induced neuronal injury

A gradual increase in iron occurs in the lesioned hippocampus after neuronal injury induced by the excitotoxin kainate, and the present study was carried out to investigate whether this increase in iron might be associated with changes in expression of the iron binding protein, ferritin. An increase in ferritin immunoreactivity was observed in glial cells of the hippocampus, as early as three days after intracerebroventricular injections of kainate. The number of ferritin positive cells peaked four weeks after the kainate injection, and decreased eight and twelve weeks after injection. They were found to be mostly microglia and oligodendrocytes by double immunofluorescence labeling with glial markers. A number of ferritin-labeled endothelial cells were also observed via electron microscopy. The decline in ferritin immunoreactivity four weeks after the injection of kainate is accompanied by an increase in the number of ferric and ferrous iron positive cells in the lesioned tissue. A substantial non-overlap between ferritin and iron-containing cells was observed. In particular, spherical ferric or ferrous iron-laden cells in the degenerating hippocampus were unlabeled for ferritin for long time periods after the kainate injection. An increase in iron, together with a reduced expression of iron binding proteins such as ferritin at long time intervals after kainate lesions, could result in a relative decrease in ferritin-induced ferroxidase activity and the presence of some of the iron in the ferrous form. It is postulated that this may contribute to chronic neuronal injury, following acute kainate-induced neurodegeneration.     

Excessive iron storage in a patient with Wilson's disease

We report on an otherwise healthy female, mother of two children, with severe decompensated liver cirrhosis due to an iron overload and Wilson's disease. The patient was considered heterozygote for hemochromatosis on the basis of the autosomal recessive inheritance for hemochromatosis, the frequency of the hemochromatosis gene, and the laboratory parameters defining her iron overload. The case is interesting because of the coincidence of Wilson's disease and excessive iron storage. Correspondence to: D. Haussinger     

Increase in ferric and ferrous iron in the rat hippocampus with time after kainate-induced excitotoxic injury

The present study aimed to elucidate the distribution of ferric and ferrous iron in the hippocampus after kainate-induced neuronal injury. A modified Perl's or Turnbull's blue histochemical stain was used to demonstrate Fe3+ and Fe2+ respectively. Very light staining for iron was observed in the hippocampus, in normal or saline-injected rats and 1-day post-kainate-injected rats. At 1 week postinjection, a number of Fe3+-positive, but very few Fe2+-positive, cells were present, in the degenerating CA fields. At 1 month postinjection, large numbers of Fe3+-positive glial cells, and some Fe2+-positive blood vessels, were observed. At 2 months postinjection, large numbers of Fe3+- and Fe2+-positive glial cells were present. The labeled cells had light and electron microscopic features of oligodendrocytes, and were double labeled with CNPase, a marker for oligodendrocytes. The observation of an increasing number of Fe3+- and Fe2+-positive cells in the degenerating hippocampus with time is consistent with the results of a nuclear microscopic study, in which an increasing amount of iron was detected in the degenerating hippocampus after kainate injection. In addition, the present study showed a shift in the oxidation state of the accumulated iron, with more cells becoming Fe2+ at a late stage. A possible consequence of the high amounts of Fe2+ in the hippocampus after kainate injection is that it could promote free radical damage in the lesioned areas.