Lipolysis-induced iron release from diferric transferrin: Possible role of lipoprotein lipase in LDL oxidation.
Conditions leading to oxidation of LDL in vivo are still unknown. While the occurrence of oxidized lipoproteins and catalytic free iron in advanced atherosclerotic lesions has been demonstrated, the origin of both is unclear. In vivo, iron metabolism is tightly regulated by iron-binding proteins that ensure that virtually no free iron exists. We examined whether physiological events such as lipolysis might reduce pH, facilitate iron release from transferrin (Tf), and promote low density lipoprotein (LDL) oxidation. Lipolysis is brought about by lipoprotein lipase (LpL), a triglyceride hydrolase present on endothelial cell surfaces and in atherosclerotic lesions. LpL hydrolysis of Intralipid lowered pH from 7.40 to 7.00 in 10% human serum and from 7.40 to 6.88 in phosphate-buffered saline. Similar decreases in pH were also observed when very low density lipoproteins were hydrolyzed by LpL. Lipolysis was accompanied by a 2-fold increase in the release of 59Fe from Tf. Tf binding to subendothelial matrix (SEM), a site of key events in atherosclerosis, increased 2-fold as the pH decreased from 7.40 to 6.00. More free iron also bound to SEM as the pH decreased below 7.40. We next tested whether a reduction in pH promotes LDL oxidation. More oxidation products were found in LDL incubated at low pH for 24 h in 10% human serum. Malonaldehyde contents (nmol/mg protein), measured as TBARS, were 7.11 +/- 0.34 at pH 7.40, 7.65 +/- 0.49 at pH 7.00, 9.00 +/- 1.18 at pH 6.50, and 11. 54 +/- 0.63 at pH 6.00. Based on these results, we hypothesize that lipolysis-induced acidic conditions enhance iron release from Tf and increase formation of oxidized LDL.
Department of Medicine, Division of Nutrition and Preventive Medicine, Columbia University College of Physicians and Surgeons, 630 West 168 Street, New York, NY 10032, USA.
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Balagopalakrishna
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Paka
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Pillarisetti
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Goldberg
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction; D014168:Transferrin / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D008077:Lipoproteins, LDL; D014168:Transferrin; D014280:Triglycerides; C028283:diferric transferrin; C099252:oxidized low density lipoprotein; D007501:Iron; D008071:Lipoprotein Lipase