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Pierre Massion
Faculty Member
Last active: 1/11/2018

Accumulation of isolevuglandin-modified protein in normal and fibrotic lung.

Mont S, Davies SS, Roberts Second LJ, Mernaugh RL, McDonald WH, Segal BH, Zackert W, Kropski JA, Blackwell TS, Sekhar KR, Galligan JJ, Massion PP, Marnett LJ, Travis EL, Freeman ML
Sci Rep. 2016 6: 24919

PMID: 27118599 · PMCID: PMC4847119 · DOI:10.1038/srep24919

Protein lysine modification by γ-ketoaldehyde isomers derived from arachidonic acid, termed isolevuglandins (IsoLGs), is emerging as a mechanistic link between pathogenic reactive oxygen species and disease progression. However, the questions of whether covalent modification of proteins by IsoLGs are subject to genetic regulation and the identity of IsoLG-modified proteins remain unclear. Herein we show that Nrf2 and Nox2 are key regulators of IsoLG modification in pulmonary tissue and report on the identity of proteins analyzed by LC-MS following immunoaffinity purification of IsoLG-modified proteins. Gene ontology analysis revealed that proteins in numerous cellular pathways are susceptible to IsoLG modification. Although cells tolerate basal levels of modification, exceeding them induces apoptosis. We found prominent modification in a murine model of radiation-induced pulmonary fibrosis and in idiopathic pulmonary fibrosis, two diseases considered to be promoted by gene-regulated oxidant stress. Based on these results we hypothesize that IsoLG modification is a hitherto unrecognized sequelae that contributes to radiation-induced pulmonary injury and IPF.

MeSH Terms (9)

Animals Chromatography, Liquid Disease Models, Animal Lung Mass Spectrometry Mice Protein Processing, Post-Translational Proteome Pulmonary Fibrosis

Connections (6)

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