論文 - 詳細
| RRC ID | 44986 |
|---|---|
| 著者 | Akaboshi T, Yamanishi R. |
| タイトル | Certain carotenoids enhance the intracellular glutathione level in a murine cultured macrophage cell line by inducing glutamate-cysteine-ligase. |
| ジャーナル | Mol Nutr Food Res |
| Abstract |
SCOPE:Glutathione (GSH) increases in RAW264 murine macrophage cells exposed to β-carotene or β-cryptoxanthin, however, the underlying mechanism has not been clarified. In the present study, we investigated the expression of glutamate-cysteine-ligase (GCL), the rate-limiting enzyme in GSH synthesis, in these cells. METHODS AND RESULTS:Both the protein and mRNA expression of GCL increased in a β-carotene concentration-dependent manner. Buthionine sulfoximine, a GCL inhibitor, abolished the β-carotene-induced GSH increase without affecting the β-carotene-induced GCL protein expression. Both cycloheximide, a translation inhibitor, and actinomycin D, a transcription inhibitor, completely suppressed the β-carotene-induced GCL protein expression and the concomitant GSH increase. Actinomycin D inhibited the β-carotene-induced Gcl mRNA expression as well. Similarly to β-carotene, β-cryptoxanthin upregulated the GCL protein expression, but lutein did not. The c-Jun N-terminal kinase (JNK) inhibitor, SP600125, suppressed the β-carotene-induced GSH increase, whereas a p38 mitogen-activated protein kinase inhibitor or an extracellular signal-regulated kinase 1/2 inhibitor did not. The JNK inhibitor also suppressed the β-carotene-induced GCL protein expression, and consistently β-carotene induced JNK phosphorylation. CONCLUSION:These findings revealed that certain carotenoids induce the Gcl mRNA expression in RAW264 cells and subsequently the GCL protein expression, which concomitantly enhances the intracellular GSH level, in a JNK pathway-related manner. |
| 巻・号 | 58(6) |
| ページ | 1291-300 |
| 公開日 | 2014-6-1 |
| DOI | 10.1002/mnfr.201300753 |
| PMID | 24668641 |
| MeSH | Animals Anthracenes / pharmacology Buthionine Sulfoximine / pharmacology Cell Line Cryptoxanthins / pharmacology* Cycloheximide / pharmacology Dactinomycin / pharmacology Enzyme Inhibitors / pharmacology Glutamate-Cysteine Ligase / genetics Glutamate-Cysteine Ligase / metabolism* Glutathione / metabolism* JNK Mitogen-Activated Protein Kinases / genetics JNK Mitogen-Activated Protein Kinases / metabolism Lutein / pharmacology Macrophages / cytology* Macrophages / drug effects* Macrophages / metabolism Mice Mitogen-Activated Protein Kinase 3 / genetics Mitogen-Activated Protein Kinase 3 / metabolism Phosphorylation RNA, Messenger / genetics RNA, Messenger / metabolism Up-Regulation beta Carotene / pharmacology* p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / metabolism |
| IF | 5.309 |
| 引用数 | 7 |
| WOS 分野 | FOOD SCIENCE & TECHNOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |