Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages1
Most models of lipoprotein oxidation by free radicals have excluded macromolecular plasma components from the system. This limits their biological significance because oxidation of lipoproteins appears to occur in the intima in the presence of a plasma ultrafiltrate. Hemin, a product of in vivo hemo...
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| Format: | Article |
| Language: | English |
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Elsevier
1998-04-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520325645 |
| _version_ | 1818647363565125632 |
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| author | Germán Camejo Carina Halberg Angela Manschik-Lundin Eva Hurt-Camejo Birgitta Rosengren Helena Olsson Göran I. Hansson Gun-Britt Forsberg Britt Ylhen |
| author_facet | Germán Camejo Carina Halberg Angela Manschik-Lundin Eva Hurt-Camejo Birgitta Rosengren Helena Olsson Göran I. Hansson Gun-Britt Forsberg Britt Ylhen |
| author_sort | Germán Camejo |
| collection | DOAJ |
| description | Most models of lipoprotein oxidation by free radicals have excluded macromolecular plasma components from the system. This limits their biological significance because oxidation of lipoproteins appears to occur in the intima in the presence of a plasma ultrafiltrate. Hemin, a product of in vivo hemoglobin degradation, binds and oxidizes purified lipoproteins. However, it is not known whether this occurs in the presence of plasma components that may sequester hemin. We found that hemin in serum diluted to protein levels of the extracellular fluid (10–30%) binds to low and high density lipoproteins (LDL, HDL) with association constants in the nmol/L range. In the presence of H2O2, hemin oxidizes both lipoproteins in diluted serum with formation of conjugated dienes, thiobarbituric acid reacting substances, and F2-isoprostanes. This appeared to be caused by the high affinity of hemin with LDL and by the Fe3+ liberated that remains associated with the particles after hemin is degraded. Spectrophotometric and fluorescence experiments and electrophoresis of porphyrins complex with LDL indicated that the heme ring is buried in the lipoprotein surface-monolayer with the carboxylic groups in contact with positive regions of the protein and the solvent. Human macrophages associated and degraded 3- to 4-times more hemin-oxidized LDL in diluted serum than native LDL. It is possible then that at sites of LDL accumulation in the extracellular intima, hemin and H2O2 production could cause oxidation with potential atherogenic consequences for cellular lipoprotein processing. This may occur even when other macromolecules of the extracellular fluid are present.—Camejo, G., C. Halberg, A. Menschik-Lundin, E. Hurt-Camejo, B. Rosengren, H. Olsson, G. I. Hansson, G-B. Forsberg, and B. Ylhen. Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages. J. Lipid Res. 1998. 39: 755–766. |
| first_indexed | 2024-12-17T01:01:21Z |
| format | Article |
| id | doaj.art-17ee3cb35b3047959689be54d8dfe029 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T01:01:21Z |
| publishDate | 1998-04-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-17ee3cb35b3047959689be54d8dfe0292022-12-21T22:09:26ZengElsevierJournal of Lipid Research0022-22751998-04-01394755766Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages1Germán Camejo0Carina Halberg1Angela Manschik-Lundin2Eva Hurt-Camejo3Birgitta Rosengren4Helena Olsson5Göran I. Hansson6Gun-Britt Forsberg7Britt Ylhen8To whom correspondence should be addressed.; Astra Hässle AB, Departments of Cell Biology and Biochemistry and Bioanalytical Chemistry, Mölndal, S-431 83 Sweden; Wallenberg Laboratory for Cardiovascular Disease, University of Gothenburg, Gothenburg, SwedenAstra Hässle AB, Departments of Cell Biology and Biochemistry and Bioanalytical Chemistry, Mölndal, S-431 83 SwedenAstra Hässle AB, Departments of Cell Biology and Biochemistry and Bioanalytical Chemistry, Mölndal, S-431 83 SwedenWallenberg Laboratory for Cardiovascular Disease, University of Gothenburg, Gothenburg, SwedenWallenberg Laboratory for Cardiovascular Disease, University of Gothenburg, Gothenburg, SwedenAstra Hässle AB, Departments of Cell Biology and Biochemistry and Bioanalytical Chemistry, Mölndal, S-431 83 SwedenAstra Hässle AB, Departments of Cell Biology and Biochemistry and Bioanalytical Chemistry, Mölndal, S-431 83 SwedenAstra Hässle AB, Departments of Cell Biology and Biochemistry and Bioanalytical Chemistry, Mölndal, S-431 83 SwedenAstra Hässle AB, Departments of Cell Biology and Biochemistry and Bioanalytical Chemistry, Mölndal, S-431 83 SwedenMost models of lipoprotein oxidation by free radicals have excluded macromolecular plasma components from the system. This limits their biological significance because oxidation of lipoproteins appears to occur in the intima in the presence of a plasma ultrafiltrate. Hemin, a product of in vivo hemoglobin degradation, binds and oxidizes purified lipoproteins. However, it is not known whether this occurs in the presence of plasma components that may sequester hemin. We found that hemin in serum diluted to protein levels of the extracellular fluid (10–30%) binds to low and high density lipoproteins (LDL, HDL) with association constants in the nmol/L range. In the presence of H2O2, hemin oxidizes both lipoproteins in diluted serum with formation of conjugated dienes, thiobarbituric acid reacting substances, and F2-isoprostanes. This appeared to be caused by the high affinity of hemin with LDL and by the Fe3+ liberated that remains associated with the particles after hemin is degraded. Spectrophotometric and fluorescence experiments and electrophoresis of porphyrins complex with LDL indicated that the heme ring is buried in the lipoprotein surface-monolayer with the carboxylic groups in contact with positive regions of the protein and the solvent. Human macrophages associated and degraded 3- to 4-times more hemin-oxidized LDL in diluted serum than native LDL. It is possible then that at sites of LDL accumulation in the extracellular intima, hemin and H2O2 production could cause oxidation with potential atherogenic consequences for cellular lipoprotein processing. This may occur even when other macromolecules of the extracellular fluid are present.—Camejo, G., C. Halberg, A. Menschik-Lundin, E. Hurt-Camejo, B. Rosengren, H. Olsson, G. I. Hansson, G-B. Forsberg, and B. Ylhen. Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages. J. Lipid Res. 1998. 39: 755–766.http://www.sciencedirect.com/science/article/pii/S0022227520325645lipoprotein oxidationhemin bindingserum componentsconjugated dienesmacrophageslipoprotein degradation |
| spellingShingle | Germán Camejo Carina Halberg Angela Manschik-Lundin Eva Hurt-Camejo Birgitta Rosengren Helena Olsson Göran I. Hansson Gun-Britt Forsberg Britt Ylhen Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages1 Journal of Lipid Research lipoprotein oxidation hemin binding serum components conjugated dienes macrophages lipoprotein degradation |
| title | Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages1 |
| title_full | Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages1 |
| title_fullStr | Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages1 |
| title_full_unstemmed | Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages1 |
| title_short | Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages1 |
| title_sort | hemin binding and oxidation of lipoproteins in serum mechanisms and effect on the interaction of ldl with human macrophages1 |
| topic | lipoprotein oxidation hemin binding serum components conjugated dienes macrophages lipoprotein degradation |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520325645 |
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