RRC ID 44914
著者 Nishio Y, Fujino M, Zhao M, Ishii T, Ishizuka M, Ito H, Takahashi K, Abe F, Nakajima M, Tanaka T, Taketani S, Nagahara Y, Li XK.
タイトル 5-Aminolevulinic acid combined with ferrous iron enhances the expression of heme oxygenase-1.
ジャーナル Int Immunopharmacol
Abstract 5-Aminolevulinic acid (5-ALA) is the naturally occurring metabolic precursor of heme. Heme negatively regulates the Maf recognition element (MARE) binding- and repressing-activity of the Bach1 transcription factor through its direct binding to Bach1. Heme oxygenase (HO)-1 is an inducible enzyme that catalyzes the rate-limiting step in the oxidative degradation of heme to free iron, biliverdin and carbon monoxide. These metabolites of heme protect against apoptosis, inflammation and oxidative stress. Monocytes and macrophages play a critical role in the initiation, maintenance and resolution of inflammation. Therefore, the regulation of inflammation in macrophages is an important target under various pathophysiological conditions. In order to address the question of what is responsible for the anti-inflammatory effects of 5-ALA, the induction of HO-1 expression by 5-ALA and sodium ferrous citrate (SFC) was examined in macrophage cell line (RAW264 cells). HO-1 expression induced by 5-ALA combined with SFC (5-ALA/SFC) was partially inhibited by MEK/ERK and p38 MAPK inhibitor. The NF-E2-related factor 2 (Nrf2) was activated and translocated from the cytosol to the nucleus in response to 5-ALA/SFC. Nrf2-specific siRNA reduced the HO-1 expression. In addition, 5-ALA/SFC increased the intracellular levels of heme in cells. The increased heme indicated that the inactivation of Bach1 by heme supports the upregulation of HO-1 expression. Taken together, our data suggest that the exposure of 5-ALA/SFC to RAW264 cells enhances the HO-1 expression via MAPK activation along with the negative regulation of Bach1.
巻・号 19(2)
ページ 300-7
公開日 2014-4-1
DOI 10.1016/j.intimp.2014.02.003
PII S1567-5769(14)00047-2
PMID 24530569
MeSH Aminolevulinic Acid / pharmacology* Animals Basic-Leucine Zipper Transcription Factors / genetics Cell Line Citric Acid Enzyme Induction Extracellular Signal-Regulated MAP Kinases / metabolism Ferrous Compounds / pharmacology* Heme Oxygenase-1 / biosynthesis* Heme Oxygenase-1 / genetics Membrane Proteins / biosynthesis* Membrane Proteins / genetics Mice RNA, Messenger / metabolism RNA, Small Interfering / genetics p38 Mitogen-Activated Protein Kinases / metabolism
IF 3.943
引用数 29
WOS 分野 PHARMACOLOGY & PHARMACY IMMUNOLOGY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)