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What Is Next in This “Age” of Heme-Driven Pathology and Protection by Hemopexin? An Update and Links with Iron

1
Department of Physiology & Biophysics, School of Medicine, University of Chile, Santiago 838-0453, Chile
2
KITE Pharma, Inc., Santa Monica, CA 90404, USA
3
Department of Biochemistry & Molecular Biology, School of Biological & Chemical Sciences, University of Missouri-Kansas City, MO 64110, USA
*
Author to whom correspondence should be addressed.
Dr. Eskew carried out this research while at the University of Missouri-Kansas City.
Pharmaceuticals 2019, 12(4), 144; https://doi.org/10.3390/ph12040144
Received: 25 July 2019 / Revised: 8 September 2019 / Accepted: 19 September 2019 / Published: 24 September 2019
(This article belongs to the Special Issue Iron as Therapeutic Targets in Human Diseases)
This review provides a synopsis of the published literature over the past two years on the heme-binding protein hemopexin (HPX), with some background information on the biochemistry of the HPX system. One focus is on the mechanisms of heme-driven pathology in the context of heme and iron homeostasis in human health and disease. The heme-binding protein hemopexin is a multi-functional protectant against hemoglobin (Hb)-derived heme toxicity as well as mitigating heme-mediated effects on immune cells, endothelial cells, and stem cells that collectively contribute to driving inflammation, perturbing vascular hemostasis and blood–brain barrier function. Heme toxicity, which may lead to iron toxicity, is recognized increasingly in a wide range of conditions involving hemolysis and immune system activation and, in this review, we highlight some newly identified actions of heme and hemopexin especially in situations where normal processes fail to maintain heme and iron homeostasis. Finally, we present preliminary data showing that the cytokine IL-6 cross talks with activation of the c-Jun N-terminal kinase pathway in response to heme-hemopexin in models of hepatocytes. This indicates another level of complexity in the cell responses to elevated heme via the HPX system when the immune system is activated and/or in the presence of inflammation. View Full-Text
Keywords: hemopexin; heme homeostasis; iron homeostasis; hemolysis; haptoglobin; ferroptosis; inflammation; biomarker; heme oxygenase; liver; microbiome; trauma; hemorrhage hemopexin; heme homeostasis; iron homeostasis; hemolysis; haptoglobin; ferroptosis; inflammation; biomarker; heme oxygenase; liver; microbiome; trauma; hemorrhage
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Montecinos, L.; Eskew, J.D.; Smith, A. What Is Next in This “Age” of Heme-Driven Pathology and Protection by Hemopexin? An Update and Links with Iron. Pharmaceuticals 2019, 12, 144.

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