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Effect of Erythropoietin, Iron Deficiency and Iron Overload on Liver Matriptase-2 (TMPRSS6) Protein Content in Mice and Rats
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SYSNO ASEP 0470081 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Effect of Erythropoietin, Iron Deficiency and Iron Overload on Liver Matriptase-2 (TMPRSS6) Protein Content in Mice and Rats Author(s) Frýdlová, J. (CZ)
Přikryl, P. (CZ)
Truksa, Jaroslav (BTO-N) RID, ORCID
Falke, L. L. (NL)
Du, X. (US)
Gurieva, I. (CZ)
Vokurka, M. (CZ)
Krijt, J. (CZ)Number of authors 8 Article number e0148540 Source Title PLoS ONE. - : Public Library of Science - ISSN 1932-6203
Roč. 11, č. 2 (2016)Number of pages 17 s. Language eng - English Country US - United States Keywords HEPCIDIN EXPRESSION ; SERINE-PROTEASE ; GENE-EXPRESSION Subject RIV EB - Genetics ; Molecular Biology R&D Projects GA13-28830S GA ČR - Czech Science Foundation (CSF) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support BTO-N - RVO:86652036 UT WOS 000369552800066 DOI 10.1371/journal.pone.0148540 Annotation 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. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2017
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