The plasma half clearance time (T1/2) of isotope-labeled rabbit hemopexin was 35.5 plus or minus 1.9 hr in rabbits. After intra-and extra-vascular equilibration of 125I-hemopexin and 131I-albumin, injection of either hematin, hemoglobin or methemoglobin (12.5 mg of heme/kg body wt) resulted in the rapid removal of 60-80% of circulating hemopexin (T1/2 = 7.2 plus or minus 0.6 hr) but did not affect albumin catabolism. After selective photo-inactivation of hemopexin, the T1/2 of this hemopexin was comparable to that of the native molecule. However, its plasma disappearance curve was not appreciably affected by administration of hematin. These findings demonstrate that hemopexin is cleared and catabolized at an enhanced rate during states of plasma heme load, and that modification of critical histidine residues of hemopexin eliminates its biological function in plasma heme disposal.
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http://dx.doi.org/10.3181/00379727-148-38575 | DOI Listing |
Free Radic Biol Med
January 2025
University of Colorado, Anschutz Medical Campus School of Medicine| Translational research laboratory of Red Blood Cell Diseases and Hypoxia related illnesses| Cardiovascular Pulmonary Research (CVP) group, Pediatrics. Electronic address:
Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.
View Article and Find Full Text PDFBiomolecules
November 2024
Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea.
Destabilization of heme proteins is recognized to play a role in acute kidney injury (AKI). Hemopexin (Hpx), known for its role in binding heme, mitigates free heme toxicity. Despite this, the potential adverse effects of Hpx deposition in kidney tissues and its impact on kidney function are not fully understood.
View Article and Find Full Text PDFFront Mol Biosci
December 2024
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States.
J Trauma Acute Care Surg
December 2024
From the Department of Surgery (J.T.R.), and Blood, Heart, Lung, and Immunology Research Center (J.T.R., K.E.R.), University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio; Department of Surgery (A.J.R., A.B., A.R.B., R.A.C.), University of California Davis, Sacramento, California; Department of Anesthesia and Critical Care (A.M., N.N.), Pontchaillou University Hospital of Rennes, Rennes, France; Department of Anesthesiology and Perioperative Medicine (J.D.R.), University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, Ohio; and Division of Pulmonary Critical Care Medicine, Department of Medicine (K.E.R.), University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Background: Cell-free hemoglobin (CFH) and free heme are potent mediators of endotheliopathy and organ injury in sepsis, but their roles in other hemolytic pathologies are not well-defined. A prime example is trauma where early hemolysis may initiate damage and predict outcome. Here, we investigated the presence of plasma CFH, heme, and their major scavengers after traumatic injury.
View Article and Find Full Text PDFPhysiol Rep
November 2024
Department of Bioengineering, University of California San Diego, San Diego, California, USA.
This study investigates hemoglobin (Hb)-induced kidney injury and the protective role of the ApoHemoglobin-Haptoglobin (ApoHb-Hp) complex against heme and Hb damage. Hb facilitates oxygen (O) delivery but poses challenges outside red blood cells (RBCs) due to toxic Hb and heme mechanisms. These are managed by binding to serum proteins like Haptoglobin (Hp) and Hemopexin (Hpx).
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