Vascular damage by unstable hemoglobins: the role of heme-depleted globin.
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.
Tsemakhovich
V A
VA
Department of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Bamm
V V
VV
Shaklai
M
M
Shaklai
N
N
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
D006242:Haptoglobins; D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D008077:Lipoproteins, LDL; D006418:Heme; D006427:Hemin; D005914:Globins; D006466:Hemopexin; D010100:Oxygen