title: Vascular damage by unstable hemoglobins: the role of heme-depleted globin.
abstract: The study compared the damage inflicted to endothelial cells (ECs) by intact hemoglobin (Hb) and isolated chains. To compare optional in vivo contact of acellular Hb with the endothelium, oxy-forms of Hb and its isolated alpha- and beta-chains existing in the thalassemias were added to primary confluent cultures of bovine aorta EC. Cell damage was followed by morphological changes or leakage of lactic dehydrogenase and pre-inserted 51Cr from the cells, followed for 27 h. Under these experimental conditions, Hb did not affect the cells but its chains inflicted damage, beta- more than alpha-chains. Based on the literature and our data, we hypothesized that hemin and/or globin should be responsible for the increased endothelial damage by beta-chains. While hemin hardly affected ECs, globin, unlike the plasma protein hemopexin, was harmful. Since hemin release leaves globin with a large hydrophobic surface, the globin-damage appears to result from adsorptive pinocytosis to endothelial membrane.
authors.affiliation: Department of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: V A
authors.initials: VA
authors.lastname: Tsemakhovich
authors.forename: V V
authors.initials: VV
authors.lastname: Bamm
authors.forename: M
authors.initials: M
authors.lastname: Shaklai
authors.forename: N
authors.initials: N
authors.lastname: Shaklai
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D002417:Cattle; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D014644:Genetic Variation; D005914:Globins / Q000737:chemistry; D006242:Haptoglobins / Q000737:chemistry; D006418:Heme / Q000737:chemistry*; D006427:Hemin / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry*; D006455:Hemoglobins, Abnormal / Q000737:chemistry; D006466:Hemopexin / Q000737:chemistry; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010873:Pinocytosis; D017434:Protein Structure, Tertiary; D013997:Time Factors
chemical_list: D006242:Haptoglobins; D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D008077:Lipoproteins, LDL; D006418:Heme; D006427:Hemin; D005914:Globins; D006466:Hemopexin; D010100:Oxygen