Lipid oxidation in human low-density lipoprotein induced by metmyoglobin/H2O2: involvement of alpha-tocopheroxyl and phosphatidylcholine alkoxyl radicals

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Lipid oxidation in human low-density lipoprotein induced by metmyoglobin/H2O2 : involvement of alpha-tocopheroxyl and phosphatidylcholine alkoxyl radicals. / Witting, P K; Willhite, C A; Davies, Michael Jonathan; Stocker, R.

In: Chemical Research in Toxicology, Vol. 12, No. 12, 12.1999, p. 1173-81.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Witting, PK, Willhite, CA, Davies, MJ & Stocker, R 1999, 'Lipid oxidation in human low-density lipoprotein induced by metmyoglobin/H2O2: involvement of alpha-tocopheroxyl and phosphatidylcholine alkoxyl radicals', Chemical Research in Toxicology, vol. 12, no. 12, pp. 1173-81.

APA

Witting, P. K., Willhite, C. A., Davies, M. J., & Stocker, R. (1999). Lipid oxidation in human low-density lipoprotein induced by metmyoglobin/H2O2: involvement of alpha-tocopheroxyl and phosphatidylcholine alkoxyl radicals. Chemical Research in Toxicology, 12(12), 1173-81.

Vancouver

Witting PK, Willhite CA, Davies MJ, Stocker R. Lipid oxidation in human low-density lipoprotein induced by metmyoglobin/H2O2: involvement of alpha-tocopheroxyl and phosphatidylcholine alkoxyl radicals. Chemical Research in Toxicology. 1999 Dec;12(12):1173-81.

Author

Witting, P K ; Willhite, C A ; Davies, Michael Jonathan ; Stocker, R. / Lipid oxidation in human low-density lipoprotein induced by metmyoglobin/H2O2 : involvement of alpha-tocopheroxyl and phosphatidylcholine alkoxyl radicals. In: Chemical Research in Toxicology. 1999 ; Vol. 12, No. 12. pp. 1173-81.

Bibtex

@article{ee66b632d58c47a8b80afc54ee742f0c,
title = "Lipid oxidation in human low-density lipoprotein induced by metmyoglobin/H2O2: involvement of alpha-tocopheroxyl and phosphatidylcholine alkoxyl radicals",
abstract = "Metmyoglobin (metMb) and H(2)O(2) can oxidize low-density lipoprotein (LDL) in vitro, and oxidized LDL may be atherogenic. The role of alpha-tocopherol (alpha-TOH) in LDL oxidation by peroxidases such as metMb is unclear. Herein, we show that during metMb/H(2)O(2)-induced oxidation of native LDL, alpha-tocopheroxyl radical (alpha-TO(*)) and hydroperoxides and alcohols of cholesteryl esters [CE-O(O)H] and phosphatidylcholine [PC-O(O)H] accumulate concomitantly with alpha-TOH consumption. The ratio of accumulating CE-O(O)H to PC-O(O)H remains constant as long as alpha-TOH is present. Accumulation of CE-O(O)H is dependent on, and correlates with, LDL's alpha-TOH content, yet does not require preformed lipid hydroperoxides or H(2)O(2). This indicates that in native LDL alpha-TOH can act as a phase-transfer agent and alpha-TO(*) as a chain-transfer agent propagating LDL lipid peroxidation via tocopherol-mediated peroxidation (TMP). After alpha-TOH depletion, CE-O(O)H continues to accumulate, albeit at a slower rate than in the presence of alpha-TOH. This second phase of LDL oxidation is accompanied by depletion of PC-OOH, a rapid increase in the CE-O(O)H/PC-O(O)H ratio, formation of lipid-derived alkoxyl radicals and phosphatidylcholine hydroxides (PC-OH), and accumulation of a second organic radical, characterized by a broad singlet EPR signal. The latter persists for several hours at 37 degrees C. We conclude that metMb/H(2)O(2)-induced peroxidation of LDL lipids occurs initially via TMP. After alpha-TOH depletion, cholesteryl esters peroxidize at higher fractional rates than surface phospholipids, and this appears to be mediated at least in part via reactions involving alkoxyl radicals derived from the peroxidatic activity of metMb on PC-OOH.",
keywords = "Adult, Electron Spin Resonance Spectroscopy, Female, Free Radicals, Humans, Hydrogen Peroxide, Lipid Peroxidation, Lipoproteins, LDL, Male, Metmyoglobin, Oxidation-Reduction, Phosphatidylcholines, Vitamin E",
author = "Witting, {P K} and Willhite, {C A} and Davies, {Michael Jonathan} and R Stocker",
year = "1999",
month = "12",
language = "English",
volume = "12",
pages = "1173--81",
journal = "Chemical Research in Toxicology",
issn = "0893-228X",
publisher = "American Chemical Society",
number = "12",

}

RIS

TY - JOUR

T1 - Lipid oxidation in human low-density lipoprotein induced by metmyoglobin/H2O2

T2 - involvement of alpha-tocopheroxyl and phosphatidylcholine alkoxyl radicals

AU - Witting, P K

AU - Willhite, C A

AU - Davies, Michael Jonathan

AU - Stocker, R

PY - 1999/12

Y1 - 1999/12

N2 - Metmyoglobin (metMb) and H(2)O(2) can oxidize low-density lipoprotein (LDL) in vitro, and oxidized LDL may be atherogenic. The role of alpha-tocopherol (alpha-TOH) in LDL oxidation by peroxidases such as metMb is unclear. Herein, we show that during metMb/H(2)O(2)-induced oxidation of native LDL, alpha-tocopheroxyl radical (alpha-TO(*)) and hydroperoxides and alcohols of cholesteryl esters [CE-O(O)H] and phosphatidylcholine [PC-O(O)H] accumulate concomitantly with alpha-TOH consumption. The ratio of accumulating CE-O(O)H to PC-O(O)H remains constant as long as alpha-TOH is present. Accumulation of CE-O(O)H is dependent on, and correlates with, LDL's alpha-TOH content, yet does not require preformed lipid hydroperoxides or H(2)O(2). This indicates that in native LDL alpha-TOH can act as a phase-transfer agent and alpha-TO(*) as a chain-transfer agent propagating LDL lipid peroxidation via tocopherol-mediated peroxidation (TMP). After alpha-TOH depletion, CE-O(O)H continues to accumulate, albeit at a slower rate than in the presence of alpha-TOH. This second phase of LDL oxidation is accompanied by depletion of PC-OOH, a rapid increase in the CE-O(O)H/PC-O(O)H ratio, formation of lipid-derived alkoxyl radicals and phosphatidylcholine hydroxides (PC-OH), and accumulation of a second organic radical, characterized by a broad singlet EPR signal. The latter persists for several hours at 37 degrees C. We conclude that metMb/H(2)O(2)-induced peroxidation of LDL lipids occurs initially via TMP. After alpha-TOH depletion, cholesteryl esters peroxidize at higher fractional rates than surface phospholipids, and this appears to be mediated at least in part via reactions involving alkoxyl radicals derived from the peroxidatic activity of metMb on PC-OOH.

AB - Metmyoglobin (metMb) and H(2)O(2) can oxidize low-density lipoprotein (LDL) in vitro, and oxidized LDL may be atherogenic. The role of alpha-tocopherol (alpha-TOH) in LDL oxidation by peroxidases such as metMb is unclear. Herein, we show that during metMb/H(2)O(2)-induced oxidation of native LDL, alpha-tocopheroxyl radical (alpha-TO(*)) and hydroperoxides and alcohols of cholesteryl esters [CE-O(O)H] and phosphatidylcholine [PC-O(O)H] accumulate concomitantly with alpha-TOH consumption. The ratio of accumulating CE-O(O)H to PC-O(O)H remains constant as long as alpha-TOH is present. Accumulation of CE-O(O)H is dependent on, and correlates with, LDL's alpha-TOH content, yet does not require preformed lipid hydroperoxides or H(2)O(2). This indicates that in native LDL alpha-TOH can act as a phase-transfer agent and alpha-TO(*) as a chain-transfer agent propagating LDL lipid peroxidation via tocopherol-mediated peroxidation (TMP). After alpha-TOH depletion, CE-O(O)H continues to accumulate, albeit at a slower rate than in the presence of alpha-TOH. This second phase of LDL oxidation is accompanied by depletion of PC-OOH, a rapid increase in the CE-O(O)H/PC-O(O)H ratio, formation of lipid-derived alkoxyl radicals and phosphatidylcholine hydroxides (PC-OH), and accumulation of a second organic radical, characterized by a broad singlet EPR signal. The latter persists for several hours at 37 degrees C. We conclude that metMb/H(2)O(2)-induced peroxidation of LDL lipids occurs initially via TMP. After alpha-TOH depletion, cholesteryl esters peroxidize at higher fractional rates than surface phospholipids, and this appears to be mediated at least in part via reactions involving alkoxyl radicals derived from the peroxidatic activity of metMb on PC-OOH.

KW - Adult

KW - Electron Spin Resonance Spectroscopy

KW - Female

KW - Free Radicals

KW - Humans

KW - Hydrogen Peroxide

KW - Lipid Peroxidation

KW - Lipoproteins, LDL

KW - Male

KW - Metmyoglobin

KW - Oxidation-Reduction

KW - Phosphatidylcholines

KW - Vitamin E

M3 - Journal article

VL - 12

SP - 1173

EP - 1181

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

SN - 0893-228X

IS - 12

ER -

ID: 138282162