Protein Modification by Endogenously Generated Lipid Electrophiles: Mitochondria as the Source and Target

被引：29

作者：

Beavers, William N. ^{[1
]}

Rose, Kristie L. ^{[2
,5
]}

Galligan, James J. ^{[2
]}

Mitchener, Michelle M. ^{[1
]}

Rouzer, Carol A. ^{[2
]}

Tallman, Keri A. ^{[1
]}

Lamberson, Connor R. ^{[1
]}

Wang, Xiaojing ^{[4
]}

Hill, Salisha ^{[5
]}

Ivanova, Pavlina T. ^{[3
]}

Brown, H. Alex ^{[2
,3
]}

Zhang, Bing ^{[4
]}

Porter, Ned A. ^{[1
]}

Marnett, Lawrence J. ^{[1
,2
,3
]}

机构：

[1] Vanderbilt Univ, AB Hancock Mem Lab Canc Res, Dept Chem,Vanderbilt Ingram Canc Ctr, Vanderbilt Inst Chem Biol,Vanderbilt Ctr Mol Toxi, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Biochem, Vanderbilt Ingram Canc Ctr, Vanderbilt Inst Chem Biol,Vanderbilt Ctr Mol Toxi, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Dept Pharmacol, Vanderbilt Ingram Canc Ctr, Vanderbilt Inst Chem Biol,Vanderbilt Ctr Mol Toxi, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Dept Biomed Informat, Vanderbilt Ingram Canc Ctr, Vanderbilt Inst Chem Biol,Vanderbilt Ctr Mol Toxi, Nashville, TN 37232 USA

[5] Vanderbilt Univ, Vanderbilt Mass Spectrometry Res Ctr, Vanderbilt Ingram Canc Ctr, Vanderbilt Inst Chem Biol,Vanderbilt Ctr Mol Toxi, Nashville, TN 37232 USA

来源：

ACS CHEMICAL BIOLOGY | 2017年 / 12卷 / 08期

基金：

美国国家卫生研究院;

关键词：

POLYUNSATURATED FATTY-ACIDS; CLICK CHEMISTRY; RAW264.7; CELLS; METABOLISM; LIPOPOLYSACCHARIDE; IDENTIFICATION; INDUCTION; GENE; PEROXIDATION; MACROPHAGES;

D O I：

10.1021/acschembio.7b00480

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Determining the impact of lipid electrophile-mediated protein damage that occurs during oxidative stress requires a comprehensive analysis of electrophile targets adducted under pathophysiological conditions. Incorporation of ?-alkynyl linoleic acid into the phospholipids of macrophages prior to activation by Kdo2-lipid A, followed by protein extraction, click chemistry, and streptavidin affinity capture, enabled a systems-level survey of proteins adducted by lipid electrophiles generated endogenously during the inflammatory response. Results revealed a dramatic enrichment for membrane and mitochondrial proteins as targets for adduction. A marked decrease in adduction in the presence of MitoTEMPO demonstrated a primary role for mitochondrial superoxide in electrophile generation and indicated an important role for mitochondria as both a source and target of lipid electrophiles, a finding that has not been revealed by prior studies using exogenously provided electrophiles.

引用

页码：2062 / 2069

页数：8

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