Induction of peroxiredoxin I gene expression by LPS involves the Src/PI3K/JNK signalling pathway

Biochimica Et Biophysica Acta
Antje BastR Walther

Abstract

Peroxiredoxin I (Prx I) belongs to a family of proteins with thiol-dependent peroxidase activity and is involved in the cellular protection against oxidative stress, the modulation of intracellular signalling cascades as well as the regulation of cell proliferation and apoptosis. In RAW 264.7 mouse macrophage cells Prx I was up-regulated on the mRNA and protein level by lipopolysaccharide (LPS). Treatment of cells with LPS increased the phosphorylation of c-Jun-NH(2) terminal kinase (JNK) and protein kinase B (PKB). Both SP600125, an inhibitor of JNK, and LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), dose-dependently decreased LPS-induced Prx I mRNA expression. Furthermore, up-regulation of Prx I mRNA by LPS was diminished by the Src tyrosine kinase inhibitor PP2 and the iNOS inhibitor L-NMMA. LPS-dependent induction of Prx I is likely mediated by an activator protein-1 site within the Prx I promoter region binding JunB and c-Fos. In contrast, NFkappaB was not involved in the activation of Prx I transcription. Our results suggest that the up-regulation of Prx I gene expression by LPS is part of the cellular response to stress and may protect against oxidative stress-related injury in RAW 264.7 cells.

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Citations

Sep 10, 2010·The Journal of Biological Chemistry·Hojin KimWoojin Jeong
Sep 28, 2010·Free Radical Biology & Medicine·Antje BastIvo Steinmetz
Jun 10, 2011·Free Radical Biology & Medicine·Saskia F ErttmannIvo Steinmetz
May 29, 2012·Free Radical Biology & Medicine·Woojin JeongSue Goo Rhee
Dec 15, 2015·Cancer Cell International·Francesca CammarotaMikko O Laukkanen
Feb 9, 2012·Molecular BioSystems·Simona D'AguannoAndrea Urbani
May 10, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sugata RoyHarukazu Suzuki
May 20, 2020·Biochemical and Biophysical Research Communications·Ying HeHuixiang Yang
Jul 3, 2021·Antioxidants·Inna L KarpenkoAlexander V Ivanov

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