Lipid aldehyde-mediated cross-linking of apolipoprotein B-100 inhibits secretion from HepG2 cells

Benjamin J Stewart; James R Roede; Jonathan A Doorn; Dennis R Petersen

doi:10.1016/j.bbalip.2009.04.004

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Lipid aldehyde-mediated cross-linking of apolipoprotein B-100 inhibits secretion from HepG2 cells

Journal article

Peer reviewed

Lipid aldehyde-mediated cross-linking of apolipoprotein B-100 inhibits secretion from HepG2 cells

Benjamin J Stewart, James R Roede, Jonathan A Doorn and Dennis R Petersen

Biochimica et biophysica acta. Molecular and cell biology of lipids, Vol.1791(8), pp.772-780

2009

DOI: 10.1016/j.bbalip.2009.04.004

PMCID: PMC2735725

PMID: 19393338

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http://doi.org/10.1016/j.bbalip.2009.04.004View

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Abstract

Hepatic oxidative stress and lipid peroxidation are common features of several prevalent disease states, including alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), a common component of the metabolic syndrome. These conditions are characterized in part by excessive accumulation of lipids within hepatocytes, which can lead to autocatalytic degradation of cellular lipids giving rise to electrophilic end products of lipid peroxidation. The pathobiology of reactive lipid aldehydes remains poorly understood. We therefore sought to investigate the effects of 4-hydroxynonenal (4-HNE) and 4-oxononenal (4-ONE) on the transport and secretion of very low-density lipoprotein using HepG2 cells as a model hepatocyte system. Physiologically relevant concentrations of 4-HNE and 4-ONE rapidly disrupted cellular microtubules in a concentration-dependent manner. Interestingly, 4-ONE reduced apolipoprotein B-100 (ApoB) secretion while 4-HNE did not significantly impair secretion. Both 4-HNE and 4-ONE formed adducts with ApoB protein, but 4-HNE adducts were detectable as mono-adducts, while 4-ONE adducts were present as protein–protein cross-links. These results demonstrate that reactive aldehydes generated by lipid peroxidation can differ in their biological effects, and that these differences can be mechanistically explained by the structures of the protein adducts formed.

4-oxononenal

Lipid peroxidation

Apolipoprotein B-100

Microtubules

4-hydroxynonenal

Details

Title: Subtitle: Lipid aldehyde-mediated cross-linking of apolipoprotein B-100 inhibits secretion from HepG2 cells
Creators: Benjamin J Stewart - Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA
James R Roede - Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA
Jonathan A Doorn - Division of Medicinal and Natural Products Chemistry, College of Pharmacy, the University of Iowa, Iowa City, IO 52242, USA
Dennis R Petersen - Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA
Resource Type: Journal article
Publication Details: Biochimica et biophysica acta. Molecular and cell biology of lipids, Vol.1791(8), pp.772-780
DOI: 10.1016/j.bbalip.2009.04.004
PMID: 19393338
PMCID: PMC2735725
NLM abbreviation: Biochim Biophys Acta Mol Cell Biol Lipids
ISSN: 1388-1981
eISSN: 1879-2618
Publisher: Elsevier B.V
Language: English
Date published: 2009
Academic Unit: Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
Record Identifier: 9984070640702771

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