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Immunoproteasome subunit β5i/LMP7-deficiency in atherosclerosis

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Item Type:Article
Title:Immunoproteasome subunit β5i/LMP7-deficiency in atherosclerosis
Creators Name:Hewing, B. and Ludwig, A. and Dan, C. and Poetzsch, M. and Hannemann, C. and Petry, A. and Lauer, D. and Görlach, A. and Kaschina, E. and Müller, D.N. and Baumann, G. and Stangl, V. and Stangl, K. and Wilck, N.
Abstract:Management of protein homeostasis by the ubiquitin-proteasome system is critical for atherosclerosis development. Recent studies showed controversial results on the role of immunoproteasome (IP) subunit {beta}5i/LMP7 in maintenance of protein homeostasis under cytokine induced oxidative stress. The present study aimed to investigate the effect of {beta}5i/LMP7-deficiency on the initiation and progression of atherosclerosis as a chronic inflammatory, immune cell driven disease. LDLR(-/-)LMP7(-/-) and LDLR(-/-) mice were fed a Western-type diet for either 6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively. Lesion burden was similar between genotypes in both stages. Macrophage content and abundance of polyubiquitin conjugates in aortic root plaques were unaltered by {beta}5i/LMP7-deficiency. In vitro experiments using bone marrow-derived macrophages (BMDM) showed that {beta}5i/LMP7-deficiency did not influence macrophage polarization or accumulation of polyubiquitinated proteins and cell survival upon hydrogen peroxide and interferon-γ treatment. Analyses of proteasome core particle composition by Western blot revealed incorporation of standard proteasome subunits in {beta}5i/LMP7-deficient BMDM and spleen. Chymotrypsin-, trypsin- and caspase-like activities assessed by using short fluorogenic peptides in BMDM whole cell lysates were similar in both genotypes. Taken together, deficiency of IP subunit {beta}5i/LMP7 does not disturb protein homeostasis and does not aggravate atherogenesis in LDLR(-/-) mice.
Keywords:Animal Disease Models, Atherosclerosis, Disease Progression, Knockout Mice, Macrophage Activation, Macrophages, Proteasome Endopeptidase Complex, Proteolysis, Animals, Mice
Source:Scientific Reports
ISSN:2045-2322
Publisher:Nature Publishing Group (U.K.)
Volume:7
Number:1
Page Range:13342
Date:17 October 2017
Official Publication:https://doi.org/10.1038/s41598-017-13592-w
PubMed:View item in PubMed

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