Tmprss6-mutated mask mice display iron deficiency anemia and high expression of hepcidin. The aim of the study was to determine the effect of erythropoietin administration on proteins participating in the control of iron homeostasis in the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6 mice, no such increase was seen in mask mice. Erythropoietin administration decreased hepcidin expression in C57BL/6 mice, but not in mask mice. Erythropoietin treatment significantly increased the spleen size in both C57BL/6 and mask mice. Furthermore, erythropoietin administration increased splenic Fam132b, Fam132a and Tfr2 mRNA content. At the protein level, erythropoietin increased the amount of splenic erythroferrone and transferrin receptor 2 both in C57BL/6 and mask mice. Splenic ferroportin content was decreased in erythropoietin-treated mask mice in comparison with erythropoietin-treated C57BL/6 mice. In mask mice, the amount of liver hemojuvelin was decreased in comparison with C57BL/6 mice. The pattern of hemojuvelin cleavage was different between C57BL/6 and mask mice: In both groups, a main hemojuvelin band was detected at approximately 52 kDa; in C57BL/6 mice, a minor cleaved band was seen at 47 kDa. In mask mice, the 47 kDa band was absent, but additional minor bands were detected at approximately 45 kDa and 48 kDa. The results provide support for the interaction between TMPRSS6 and hemojuvelin in vivo; they also suggest that hemojuvelin could be cleaved by another as yet unknown protease in the absence of functional TMPRSS6. The lack of effect of erythropoietin on hepcidin expression in mask mice can not be explained by changes in erythroferrone synthesis, as splenic erythroferrone content increased after erythropoietin administration in both C57BL/6 and mask mice.

• MeSH
• cytokiny genetika   metabolismus   MeSH
• erythropoetin genetika   farmakologie   MeSH
• GPI-vázané proteiny MeSH
• hepcidiny genetika   metabolismus   MeSH
• játra metabolismus   patologie   MeSH
• membránové proteiny genetika   metabolismus   MeSH
• mutantní kmeny myší MeSH
• myši MeSH
• protein hemochromatózy MeSH
• proteiny vázající RNA genetika   metabolismus   MeSH
• regulace genové exprese účinky léků   genetika   MeSH
• serinové endopeptidasy genetika   metabolismus   MeSH
• slezina metabolismus   patologie   MeSH
• svalové proteiny genetika   metabolismus   MeSH
• velikost orgánu účinky léků   genetika   MeSH
• železo metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Ankrd17 protein, mouse MeSH Prohlížeč
• cytokiny MeSH
• Erfe protein, mouse MeSH Prohlížeč
• erythropoetin MeSH
• GPI-vázané proteiny MeSH
• Hamp protein, mouse MeSH Prohlížeč
• hepcidiny MeSH
• HJV protein, mouse MeSH Prohlížeč
• matriptase 2 MeSH Prohlížeč
• membránové proteiny MeSH
• protein hemochromatózy MeSH
• proteiny vázající RNA MeSH
• serinové endopeptidasy MeSH
• svalové proteiny MeSH
• železo MeSH

Matriptase-2 (TMPRSS6) is an important negative regulator of hepcidin expression; however, the effects of iron overload or accelerated erythropoiesis on liver TMPRSS6 protein content in vivo are largely unknown. We determined TMPRSS6 protein content in plasma membrane-enriched fractions of liver homogenates by immunoblotting, using a commercial antibody raised against the catalytic domain of TMPRSS6. Plasma membrane-enriched fractions were obtained by centrifugation at 3000 g and washing. TMPRSS6 was detected in the 3000 g fraction as a 120 kDa full-length protein in both mice and rats. Feeding of iron-deficient diet as well as erythropoietin treatment increased TMPRSS6 protein content in rats and mice by a posttranscriptional mechanism; the increase in TMPRSS6 protein by erythropoietin was also observed in Bmp6-mutant mice. Administration of high doses of iron to mice (200, 350 and 700 mg/kg) decreased TMPRSS6 protein content. Hemojuvelin was detected in the plasma membrane-enriched fractions of control animals as a full length protein of approximately 52 kDa; in iron deficient animals, the full length protein was partially cleaved at the N-terminus, resulting in an additional weak band of approximately 47 kDa. In livers from hemojuvelin-mutant mice, TMPRSS6 protein content was strongly decreased, suggesting that intact hemojuvelin is necessary for stable TMPRSS6 expression in the membrane. Overall, the results demonstrate posttranscriptional regulation of liver TMPRSS6 protein by iron status and erythropoietin administration, and provide support for the interaction of TMPRSS6 and hemojuvelin proteins in vivo.

• MeSH
• anemie z nedostatku železa metabolismus   MeSH
• deficit železa * MeSH
• erythropoetin metabolismus   farmakologie   MeSH
• GPI-vázané proteiny MeSH
• játra účinky léků   metabolismus   MeSH
• kostní morfogenetický protein 6 genetika   MeSH
• krysa rodu Rattus MeSH
• membránové proteiny metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• mutace MeSH
• myši knockoutované MeSH
• myši MeSH
• přetížení železem metabolismus   MeSH
• protein hemochromatózy MeSH
• serinové endopeptidasy metabolismus   MeSH
• sodíko-draslíková ATPasa metabolismus   MeSH
• železo metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• erythropoetin MeSH
• GPI-vázané proteiny MeSH
• HJV protein, mouse MeSH Prohlížeč
• kostní morfogenetický protein 6 MeSH
• matriptase 2 MeSH Prohlížeč
• membránové proteiny MeSH
• protein hemochromatózy MeSH
• serinové endopeptidasy MeSH
• sodíko-draslíková ATPasa MeSH
• železo MeSH