Taurine chloramine induces heme oxygenase-1 expression via Nrf2 activation in murine macrophages.
Taurine chloramine (TauCl) is produced abundantly in activated neutrophils by a reaction between the stored taurine and the newly produced HOCl by the myeloperoxidase system, and is much less oxidizing or toxic than HOCl. TauCl has been shown to provide cytoprotection against inflammatory tissue injury by inhibiting the overproduction of inflammatory mediators. The result of this study shows that TauCl upregulated the expression of heme oxygenase (HO)-1 and increased HO activity in RAW 264.7 macrophages, while taurine had no effect. TauCl by itself generated reactive oxygen species (ROS) in macrophages and diminished total glutathione (GSH) level initially. TauCl increased the nuclear translocation of NF-E2-related factor 2 (Nrf2) and enhanced its binding to the anti-oxidant response element (ARE). This, in turn, was responsible for the upregulation of HO-1 expression. In summary, TauCl generated ROS in RAW 264.7 macrophages and decreased cellular GSH level initially. This was responsible for the nuclear translocation of Nrf2 and its binding to ARE promoted the expression of HO-1 and increased HO activity. Thus, TauCl-derived elevation of HO activity may play an essential role in the adaptive cytoprotection of inflammatory tissues.
Kim
Chaekyun
C
Laboratory for Leukocyte Signaling Research, Inha University School of Medicine, Incheon 400-712, Republic of Korea. chaekyun@inha.ac.kr
Jang
Jin Sun
JS
Cho
Mi-Ran
MR
Agarawal
Santosh R
SR
Cha
Young-Nam
YN
D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005452:Fluoresceins / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014178:Translocation, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D004791:Enzyme Inhibitors; D005452:Fluoresceins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013654:Taurine; C029569:diacetyldichlorofluorescein; D009569:Nitric Oxide; C043410:N-chlorotaurine; D051547:Heme Oxygenase-1; D005978:Glutathione