Upregulation and Mitochondrial Sequestration of Hemoglobin Occur in Circulating Leukocytes during Critical Illness, Conferring a Cytoprotective Phenotype

Molecular Medicine
Attila BrunyanszkiCsaba Szabo

Abstract

The classical role of hemoglobin in the erythrocytes is to carry oxygen from the lungs to the tissues via the circulation. However, hemoglobin also acts as a redox regulator and as a scavenger of the gaseous mediators nitric oxide (NO) and hydrogen sulfide (H2S). Here we show that upregulation of hemoglobin (α, β and δ variants of globin proteins) occurs in human peripheral blood mononuclear cells (PBMCs) in critical illness (patients with severe third-degree burn injury and patients with sepsis). The increase in intracellular hemoglobin concentration is a result of a combination of enhanced protein expression and uptake from the extra-cellular space via a CD163-dependent mechanism. Intracellular hemoglobin preferentially localizes to the mitochondria, where it interacts with complex I and, on the one hand, increases mitochondrial respiratory rate and mitochondrial membrane potential, and on the other hand, protects from H2O2-induced cytotoxicity and mitochondrial DNA damage. Both burn injury and sepsis were associated with increased plasma levels of H2S. Incubation of mononuclear cells with H2S induced hemoglobin mRNA upregulation in PBMCs in vitro. Intracellular hemoglobin upregulation conferred a protective effect against ce...Continue Reading

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Citations

Jan 17, 2019·Journal of Burn Care & Research : Official Publication of the American Burn Association·Akbar AhmadCsaba Szabo
Aug 10, 2019·NPJ Systems Biology and Applications·Giuseppe Gianini Figuerêido LeiteReinaldo Salomão
Jun 28, 2019·ACS Applied Materials & Interfaces·Yuping LiangXing Wang
Sep 11, 2021·Frontiers in Immunology·Afshin DerakhshaniVito Racanelli
Oct 22, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhihong ZhengYueling Zhang

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