RRC ID 39817
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