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Catalase induces the expression of inducible nitric oxide synthase through activation of NF-κB and PI3K signaling pathway in Raw 264.7 cells

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Author(s)
Byeong-Churl JangJi-Hye PaikSang-Pyo KimJae-Hoon BaeKyo-Chul MunDae-Kyu SongChi-Heum ChoDong-Hoon ShinTaeg Kyu KwonJong-Wook ParkJong-Gu ParkWon-Ki BaekMin-Ho SuhSoo Hwan LeeSuk-Hwan BaekIn-Seon LeeSeong-Il Suh
Keimyung Author(s)
Jang, Byeong ChurlKim, Sang PyoBae, Jae HoonMun, Kyo CheolSong, Dae KyuCho, Chi HeumShin, Dong HoonKwon, Taeg KyuPark, Jong WookPark, Jong GuBaek, Won KiSuh, Min HoSuh, Seong Il
Department
Dept. of Molecular Medicine (분자의학)
Dept. of Pathology (병리학)
Dept. of Physiology (생리학)
Dept. of Biochemistry (생화학)
Dept. of Obstetrics & Gynecology (산부인과학)
Dept. of Preventive Medicine (예방의학)
Dept. of Immunology (면역학)
Dept. of Microbiology (미생물학)
Institute for Medical Science(의과학연구소)
Journal Title
Biochemical Pharmacology
Issued Date
2004
Volume
68
Issue
11
Abstract
It has been reported that macrophages produce substantial amounts of nitrite and nitrate after addition of catalase, but the mechanism
associated remains unclear. In present study, we investigated whether catalase modulates the expression of inducible nitric oxide synthase
(iNOS), an enzyme that produces nitric oxide. Exposure of Raw 264.7 macrophages (Raw cells) to catalase induced high expression of
iNOS mRNA as well as protein with enzymatic activity. Data of mechanical analyses, such as iNOS promoter-driven luciferase assay and
actinomycin D chase experiments demonstrated that the induction was due to increased iNOS transcription and post-transcriptional iNOS
mRNA stability. Of interest, catalase-induced iNOS protein expression was abrogated through inactivation of NF-kB pathway by MG132
or BAY 11-7085 and PI3K pathway by LY294002 or wortmannin, respectively. In particular, blockage of PI3K pathway by LY294002
down-regulated iNOS transcription and steady-state iNOS mRNA levels as well as iNOS mRNA stability induced by catalase, suggesting
regulation of PI3K pathway in catalase-induced iNOS expression at the levels of iNOS transcription, steady-state mRNA status, and
mRNA stability. Additional cell culture works in different types of cells indicated that iNOS expression by catalase might be cell typespecific,
based on the facts that catalase induced iNOS expression in BV2 microglial macrophage-like cells, but not in HT-29 or A549,
human colon or lung cancer epithelial-like cells. Together, these results demonstrate for the first time that catalase induces iNOS
expression in Raw cells, which seems to be associated with the increase of iNOS transcription and mRNA stability as well as the activation
of NF-kB and PI3K signaling pathways.
# 2004 Elsevier Inc. All rights reserved.
Keywords: Catalase; iNOS; NF-kB; PI3K; Raw 264.7 cells; Classification: Molecular and cellular pharmacology
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