論文 - 詳細
RRC ID | 39817 |
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著者 | Teshima K, Yamamoto A, Yamaoka K, Honda Y, Honda S, Sasaki T, Kojima S. |
タイトル | Involvement of calcium ion in elevation of mRNA for gamma-glutamylcysteine synthetase (gamma-GCS) induced by low-dose gamma-rays. |
ジャーナル | Int J Radiat Biol |
Abstract |
PURPOSE:To investigate the mechanism of the intracellular glutathione elevation induced by low-dose gamma-radiation. MATERIALS AND METHODS:RAW 264.7 cells were irradiated with 1-400cGy gamma-rays. Intracellular total glutathione content was determined by DTNB-recycling assay. Expression of mRNA for intracellular glutathione synthesis-related enzymes with or without treatment with various inhibitors of second messengers of gene expression were examined by Northern blot analysis. RESULTS:Expression of mRNA for gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme of the de novo glutathione synthesis pathway, was elevated much more than that of glutathione reductase (GR) mRNA after exposure to 50cGy gamma-rays. The low-dose gamma-ray-induced gamma-GCS mRNA elevation was abolished by inhibitors of protein kinase C and protein tyrosine kinase, as well as by the calcium ion channel blocker, nifedipine. Calcium-related reagents, such BAPTA/AM and EGTA, chelators of intra- and extracellular Ca2+ respectively, and a Ca2+ ionophore (A23187), also strongly blocked the elevation of gamma-GCS mRNA expression induced by gamma-rays. CONCLUSIONS:The increase of intracellular glutathione in RAW 264.7 soon after low-dose gamma-ray exposure mainly occurs through the operation of the de novo pathway, following by the induction of gamma-GCS mRNA, for which elevation of intracellular calcium is required. |
巻・号 | 76(12) |
ページ | 1631-9 |
公開日 | 2000-12-1 |
DOI | 10.1080/09553000050201127 |
PMID | 11133045 |
MeSH | Animals Blotting, Northern Calcimycin / pharmacology Calcium / metabolism* Calcium Channel Blockers / pharmacology Cell Line Chelating Agents / pharmacology Dose-Response Relationship, Radiation Egtazic Acid / analogs & derivatives Egtazic Acid / pharmacology Gamma Rays* Glutamate-Cysteine Ligase / metabolism* Glutathione / metabolism Glutathione Reductase / metabolism Ionophores / pharmacology Ions* Macrophages / radiation effects Mice Models, Biological Nifedipine / pharmacology Protein Kinase C / antagonists & inhibitors Protein-Tyrosine Kinases / antagonists & inhibitors RNA, Messenger / radiation effects* Signal Transduction / radiation effects Time Factors |
IF | 2.368 |
引用数 | 20 |
WOS 分野 | NUCLEAR SCIENCE & TECHNOLOGY RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING BIOLOGY |
リソース情報 | |
ヒト・動物細胞 |