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Deregulation of Hepatic Mek1/2–Erk1/2 Signaling Module in Iron Overload Conditions

1
Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm 89081, Germany
2
Department of Medicine III and IZKF, University Hospital Aachen, Aachen 52074, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceuticals 2019, 12(2), 70; https://doi.org/10.3390/ph12020070
Received: 25 February 2019 / Revised: 30 April 2019 / Accepted: 5 May 2019 / Published: 7 May 2019
(This article belongs to the Special Issue Iron as Therapeutic Targets in Human Diseases)
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Abstract

The liver, through the production of iron hormone hepcidin, controls body iron levels. High liver iron levels and deregulated hepcidin expression are commonly observed in many liver diseases including highly prevalent genetic iron overload disorders. In spite of a number of breakthrough investigations into the signals that control hepcidin expression, little progress has been made towards investigations into intracellular signaling in the liver under excess of iron. This study examined hepatic signaling pathways underlying acquired and genetic iron overload conditions. Our data demonstrate that hepatic iron overload associates with a decline in the activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) kinase (Mek1/2) pathway by selectively affecting the phosphorylation of Erk1/2. We propose that Mek1/2-Erk1/2 signaling is uncoupled from iron-Bmp-Smad-mediated hepcidin induction and that it may contribute to a number of liver pathologies in addition to toxic effects of iron. We believe that our findings will advance the understanding of cellular signaling events in the liver during iron overload of different etiologies. View Full-Text
Keywords: liver; iron; hepcidin; Mek/Erk; Hfe; Bmp/Smad liver; iron; hepcidin; Mek/Erk; Hfe; Bmp/Smad
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Tangudu, N.K.; Buth, N.; Strnad, P.; Cirstea, I.C.; Spasić, M.V. Deregulation of Hepatic Mek1/2–Erk1/2 Signaling Module in Iron Overload Conditions. Pharmaceuticals 2019, 12, 70.

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