TY - JOUR
T1 - Involvement of calcium ion in elevation of mRNA for γ-glutamylcysteine synthetase (γ-GCS) induced by low-dose γ-rays
AU - Teshima, K.
AU - Yamamoto, A.
AU - Yamaoka, K.
AU - Honda, Y.
AU - Honda, S.
AU - Sasaki, T.
AU - Kojima, S.
N1 - Funding Information:
This work was supported inpart by aGrant-in-Aid for ScientiŽ c Research (1810)6fr5omt5he6 Ministry of Education, Science, Sports and Culture of Japan. The authors are also grateful to Yoko Honda and Shuji Honda (Tokyo Metropolitan Institute of Gerontology) for technical suggestions.
PY - 2000
Y1 - 2000
N2 - Purpose: To investigate the mechanism of the intracellular glutathione elevation induced by low-dose γ-radiation. Materials and methods: RAW 264.7 cells were irradiated with 1-400cGy γ-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 γ-glutamylcysteine synthetase (γ-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 γ-rays. The low-dose γ-ray-induced γ-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 γ-GCS mRNA expression induced by γ-rays. Conclusions: The increase of intracellular glutathione in RAW 264.7 soon after low-dose γ-ray exposure mainly occurs through the operation of the de novo pathway, following by the induction of γ-GCS mRNA, for which elevation of intracellular calcium is required.
AB - Purpose: To investigate the mechanism of the intracellular glutathione elevation induced by low-dose γ-radiation. Materials and methods: RAW 264.7 cells were irradiated with 1-400cGy γ-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 γ-glutamylcysteine synthetase (γ-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 γ-rays. The low-dose γ-ray-induced γ-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 γ-GCS mRNA expression induced by γ-rays. Conclusions: The increase of intracellular glutathione in RAW 264.7 soon after low-dose γ-ray exposure mainly occurs through the operation of the de novo pathway, following by the induction of γ-GCS mRNA, for which elevation of intracellular calcium is required.
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U2 - 10.1080/09553000050201127
DO - 10.1080/09553000050201127
M3 - Article
C2 - 11133045
AN - SCOPUS:0033638618
VL - 76
SP - 1631
EP - 1639
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
SN - 0955-3002
IS - 12
ER -