HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Balagopalakrishna, C. Articles by Goldberg, I. J. Search for Related Content PubMed PubMed Citation Articles by Balagopalakrishna, C. Articles by Goldberg, I. J. Social Bookmarking                      What's this?

The Journal of Lipid Research, Vol. 40, 1347-1356, July 1999
Copyright © 1999 by Lipid Research, Inc.

Original Article

Lipolysis-induced iron release from diferric transferrin: possible role of lipoprotein lipase in LDL oxidation

Correspondence to: Ira J. Goldberg

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.—Balagopalakrishna, C., L. Paka, S. Pillarisetti, and I. J. Goldberg. Lipolysis-induced iron release from diferric transferrin: possible role of lipoprotein lipase in LDL oxidation. J. Lipid Res. 1999. 40: 1347;–1356.

Supplementary key words: atherosclerosis, lipoprotein lipase, triglycerides, fatty acids, proteoglycans

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Singh and P. Wangemann Free radical stress-mediated loss of Kcnj10 protein expression in stria vascularis contributes to deafness in Pendred syndrome mouse model Am J Physiol Renal Physiol, January 1, 2008; 294(1): F139 - F148. [Abstract] [Full Text] [PDF]

				B. Singh, D. Charkowicz, and D. Mascarenhas Insulin-like Growth Factor-independent Effects Mediated by a C-terminal Metal-binding Domain of Insulin-like Growth Factor Binding Protein-3 J. Biol. Chem., January 2, 2004; 279(1): 477 - 487. [Abstract] [Full Text] [PDF]

				V. R. Babaev, M. B. Patel, C. F. Semenkovich, S. Fazio, and M. F. Linton Macrophage Lipoprotein Lipase Promotes Foam Cell Formation and Atherosclerosis in Low Density Lipoprotein Receptor-deficient Mice J. Biol. Chem., August 18, 2000; 275(34): 26293 - 26299. [Abstract] [Full Text] [PDF]