RESUMO
Mg deficiency increases the concentration of Zn in the liver. We investigated the effect of Mg deficiency on the expression of Zn-regulating factors such as Zn transporters and metallothionein (MT) in the rat liver. Because Ca deficiency alleviates some of the effects of Mg deficiency, we also investigated the interactions associated with Ca and Mg deficiencies. Growing male rats were given a control diet, a Mg-deficient diet, a Ca-deficient diet and a Mg- and Ca-deficient diet for 3 weeks. Mg and Ca deficiencies additively increased the mRNA levels of MT-1 and MT-2, the MT protein concentration and the concentration of Zn in the liver. The hepatic mRNA level of Zip14 increased with Mg deficiency but not with Ca deficiency. The dietary treatments did not affect the mRNA levels of other Zn transporters such as Zip1, Zip5, ZnT1, ZnT5 and ZnT6 in the liver. Ca deficiency was found to decrease the amount of femoral Zn and increase serum Zn concentration. This did not occur in the case of Mg deficiency. These results suggest that Mg deficiency enhances hepatic Zn uptake by the up-regulation of Zip14 expression and increases hepatic Zn concentration, leading to the enhancement of MT expression. Ca deficiency causes a transfer of Zn from the bone to the liver, which increases hepatic Zn concentration and, in turn, up-regulates the expression of MT. Because Mg and Ca deficiencies increase hepatic Zn concentration and increase MT expression by different mechanisms, their effects are additive.
Assuntos
Cálcio/deficiência , Proteínas de Transporte de Cátions/biossíntese , Fígado/metabolismo , Deficiência de Magnésio/metabolismo , Metalotioneína/biossíntese , Zinco/metabolismo , Animais , Transporte Biológico , Reabsorção Óssea/etiologia , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Dermatite/etiologia , Fêmur/metabolismo , Deficiência de Magnésio/complicações , Deficiência de Magnésio/imunologia , Deficiência de Magnésio/fisiopatologia , Masculino , Metalotioneína/genética , Metalotioneína/metabolismo , Estresse Oxidativo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Pele/imunologia , Pele/metabolismo , Organismos Livres de Patógenos Específicos , Regulação para Cima , Zinco/sangueRESUMO
Mg deficiency accelerates Fe accumulation in the liver, which may induce various metabolic disturbances. In the present study, we examined the gene expression of Hepcidin, a peptide hormone produced in the liver to regulate intestinal Fe absorption negatively, in Mg-deficient rats. Although liver Fe concentration was significantly higher in rats fed an Mg-deficient diet for 4 weeks than in rats fed a control diet, Hepcidin expression in the liver was comparable between the dietary groups. Previous studies revealed that Fe overload up-regulated Hepcidin expression through transcriptional activation by Fe-induced bone morphogenetic protein (Bmp) 6, a growth/differentiation factor belonging to the transforming growth factor-ß family, in the liver. Mg deficiency up-regulated the expression of Bmp6 but did not affect the expression of inhibition of DNA binding 1, a sensitive Bmp-responsive gene. In addition, the expression of Bmp receptors such as activin receptor-like kinase 2 (Alk2), activin receptor type IIA (Actr2a), activin receptor type IIB (Actr2b) and Bmp type II receptor (Bmpr2) was lower in the liver of Mg-deficient rats than in that of control rats. The present study indicates that accumulation of hepatic Fe by Mg deficiency is a stimulant inducing Bmp6 expression but not Hepcidin expression by blunting Bmp signalling possibly resulting from down-regulation of the receptor expression. Unresponsive Hepcidin expression may have a role in Mg deficiency-induced changes related to increased liver Fe.
Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Fígado/metabolismo , Deficiência de Magnésio/genética , Deficiência de Magnésio/metabolismo , Animais , Sequência de Bases , Proteína Morfogenética Óssea 6/genética , Receptores de Proteínas Morfogenéticas Ósseas/genética , Primers do DNA/genética , Proteínas Ligadas por GPI , Proteína da Hemocromatose , Hepcidinas , Antígenos de Histocompatibilidade Classe I/genética , Proteína 1 Inibidora de Diferenciação/genética , Ferro/metabolismo , Magnésio/sangue , Masculino , Proteínas de Membrana/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores da Transferrina/genética , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Magnesium (Mg) deficiency is well known to affect metabolism of some trace minerals. We investigated the effect of Mg deficiency on hepatic concentration of various minerals in rats. Twelve 5-week-old male rats were divided into the groups given a control diet and an Mg-deficient diet. After 4 weeks, liver sample was collected from each rat. The concentrations of 36 minerals were simultaneously determined by a semiquantitative method of inductively coupled plasma-mass spectrometry (ICP-MS). The semiquantitative analysis showed that Mg deficiency significantly increased iron (Fe), copper (Cu), zinc (Zn), gallium (Ga), yttrium (Y), zirconium (Zr), molybdenum (Mo), rhodium (Rh), silver (Ag), and barium (Ba) concentrations, and significantly decreased scandium (Sc) and niobium (Nb) concentrations in rat liver. Then, hepatic Fe, Cu, Zn, Sc, Zr, and Mo concentrations were quantitatively measured, which indicated the similar effects as observed by the semiquantitative analysis. Additionally, the semiquantitative measurements of these minerals were highly correlated to these measurements with the quantitative method, but the measurements were not completely consistent between these analyses. The present study is the first research indicating the changes of hepatic Ga, Y, Zr, Mo, Rh, Ag, Ba, Sc, and Nb concentrations in Mg-deficient rats. The present study also indicates that the semiquantitative analysis with ICP-MS is a valid method for screening analysis to investigate various mineral concentrations in animal tissues.
