LDL protein nitration: implication for LDL protein unfolding.

Archives of Biochemistry and Biophysics
Ryan T HamiltonTzung K Hsiai

Abstract

Oxidatively- or enzymatically-modified low-density lipoprotein (LDL) is intimately involved in the initiation and progression of atherosclerosis. The in vivo modified LDL is electro-negative (LDL(-)) and consists of peroxidized lipid and unfolded apoB-100 protein. This study was aimed at establishing specific protein modifications and conformational changes in LDL(-) assessed by liquid chromatography/tandem mass spectrometry (LC/MS/MS) and circular dichroism analyses, respectively. The functional significance of these chemical modifications and structural changes were validated with binding and uptake experiments to- and by bovine aortic endothelial cells (BAEC). The plasma LDL(-) fraction showed increased nitrotyrosine and lipid peroxide content as well as a greater cysteine oxidation as compared with native- and total-LDL. LC/MS/MS analyses of LDL(-) revealed specific modifications in the apoB-100 moiety, largely involving nitration of tyrosines in the alpha-helical structures and beta(2) sheet as well as cysteine oxidation to cysteic acid in beta(1) sheet. Circular dichroism analyses showed that the alpha-helical content of LDL(-) was substantially lower ( approximately 25%) than that of native LDL ( approximately 90%); conv...Continue Reading

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Citations

Sep 4, 2009·Archives of Pharmacal Research·Jung Rok LeeKwang Pyo Kim
Feb 23, 2010·Chemical Research in Toxicology·Silvina BartesaghiRafael Radi
Aug 29, 2013·Mediators of Inflammation·Cédric DelporteKarim Zouaoui Boudjeltia
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Nov 19, 2019·Archives of Biochemistry and Biophysics·Mauricio MastrogiovanniHomero Rubbo
May 13, 2021·Nature Communications·Andrea de la Fuente-AlonsoJuan Miguel Redondo
May 12, 2021·Nature Reviews. Nephrology·Heidi NoelsJoachim Jankowski
Feb 6, 2018·Chemical Reviews·Gerardo Ferrer-SuetaRafael Radi

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