Catalase induces the expression of inducible nitric oxide synthase through activation of NF-κB and PI3K signaling pathway in Raw 264.7 cells
- 장병철; 김상표; 배재훈; 문교철; 송대규; 조치흠; 신동훈; 권택규; 박종욱; 박종구; 백원기; 서민호; 서성일
- Alternative Author(s)
- Jang, Byeong Churl; Kim, Sang Pyo; Bae, Jae Hoon; Mun, Kyo Cheol; Song, Dae Kyu; Cho, Chi Heum; Shin, Dong Hoon; Kwon, Taeg Kyu; Park, Jong Wook; Park, Jong Gu; Baek, Won Ki; Suh, Min Ho; Suh, Seong Il
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- 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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