Abstract
First, we determined the cerebral localization of reduced glutathione (GSH) in normal mice by means of autoradiography using 99mTc-meso- hexamethyl propylene oxime. A highly specific localization of GSH in the cerebellum and hippocampus was observed. Secondly, we measured the elevation of GSH level in the brain after low-dose γ-irradiation. The cerebral GSH levels increased soon after irradiation with 50 cGy of γ-rays, reaching a maximum at 3 h post-treatment, then remaining significantly higher than that of the non-irradiated control until 12 h and returning to the control level by 24 h. Thirdly, we examined the induction of the activities and the mRNAs of proteins involved in the synthesis and regeneration of GSH in the brain of mice subjected to low-dose γ-ray irradiation. The level of mRNA for γ- glutamylcysteine synthetase was significantly increased at 0.5 h, and remained high until 2 h post-irradiation (50 cGy). The level was transiently lowered to the non-irradiated control level at 3 h and slightly increased again after 6 h post-irradiation. γ-Glutamylcysteine synthetase activity was significantly increased 3 h after irradiation, and remained high up to 24 h post-irradiation. As for glutathione reductase, the mRNA level was increased at 0.5 h, and peaked strongly at 2 h, while the enzyme activity was significantly increased at 6 h after irradiation, and continued to increase up to 24 h. The level of mRNA for thioredoxin, which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked between 0.5 h and 2 h post-irradiation, and rapidly declined thereafter. The content of thioredoxin showed a transient decrease immediately after irradiation, but was then remarkably elevated, reaching a maximum at 3 h, and thereafter declining sharply. These results indicate that the increase in endogenous GSH in mouse brain soon after low-dose γ-ray irradiation is a consequence of the induction of GSH synthesis-related proteins and occurs via both the de novo synthesis and the regeneration pathways.
| Original language | English |
|---|---|
| Pages (from-to) | 262-269 |
| Number of pages | 8 |
| Journal | Brain Research |
| Volume | 808 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Oct 19 1998 |
| Externally published | Yes |
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Keywords
- Glutathione
- Low-dose γ-ray
- Mouse brain
- mRNA for glutathione reductase
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Localization of glutathione and induction of glutathione synthesis- related proteins in mouse brain by low doses of γ-rays. / Kojima, Shuji; Matsuki, Osamu; Nomura, Takaharu; Shimura, Noriko; Kubodera, Akiko; Yamaoka, Kiyonori; Tanooka, Hiroshi; Wakasugi, Hiro; Honda, Yoko; Honda, Shuji; Sasaki, Toru.
In: Brain Research, Vol. 808, No. 2, 19.10.1998, p. 262-269.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Localization of glutathione and induction of glutathione synthesis- related proteins in mouse brain by low doses of γ-rays
AU - Kojima, Shuji
AU - Matsuki, Osamu
AU - Nomura, Takaharu
AU - Shimura, Noriko
AU - Kubodera, Akiko
AU - Yamaoka, Kiyonori
AU - Tanooka, Hiroshi
AU - Wakasugi, Hiro
AU - Honda, Yoko
AU - Honda, Shuji
AU - Sasaki, Toru
PY - 1998/10/19
Y1 - 1998/10/19
N2 - First, we determined the cerebral localization of reduced glutathione (GSH) in normal mice by means of autoradiography using 99mTc-meso- hexamethyl propylene oxime. A highly specific localization of GSH in the cerebellum and hippocampus was observed. Secondly, we measured the elevation of GSH level in the brain after low-dose γ-irradiation. The cerebral GSH levels increased soon after irradiation with 50 cGy of γ-rays, reaching a maximum at 3 h post-treatment, then remaining significantly higher than that of the non-irradiated control until 12 h and returning to the control level by 24 h. Thirdly, we examined the induction of the activities and the mRNAs of proteins involved in the synthesis and regeneration of GSH in the brain of mice subjected to low-dose γ-ray irradiation. The level of mRNA for γ- glutamylcysteine synthetase was significantly increased at 0.5 h, and remained high until 2 h post-irradiation (50 cGy). The level was transiently lowered to the non-irradiated control level at 3 h and slightly increased again after 6 h post-irradiation. γ-Glutamylcysteine synthetase activity was significantly increased 3 h after irradiation, and remained high up to 24 h post-irradiation. As for glutathione reductase, the mRNA level was increased at 0.5 h, and peaked strongly at 2 h, while the enzyme activity was significantly increased at 6 h after irradiation, and continued to increase up to 24 h. The level of mRNA for thioredoxin, which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked between 0.5 h and 2 h post-irradiation, and rapidly declined thereafter. The content of thioredoxin showed a transient decrease immediately after irradiation, but was then remarkably elevated, reaching a maximum at 3 h, and thereafter declining sharply. These results indicate that the increase in endogenous GSH in mouse brain soon after low-dose γ-ray irradiation is a consequence of the induction of GSH synthesis-related proteins and occurs via both the de novo synthesis and the regeneration pathways.
AB - First, we determined the cerebral localization of reduced glutathione (GSH) in normal mice by means of autoradiography using 99mTc-meso- hexamethyl propylene oxime. A highly specific localization of GSH in the cerebellum and hippocampus was observed. Secondly, we measured the elevation of GSH level in the brain after low-dose γ-irradiation. The cerebral GSH levels increased soon after irradiation with 50 cGy of γ-rays, reaching a maximum at 3 h post-treatment, then remaining significantly higher than that of the non-irradiated control until 12 h and returning to the control level by 24 h. Thirdly, we examined the induction of the activities and the mRNAs of proteins involved in the synthesis and regeneration of GSH in the brain of mice subjected to low-dose γ-ray irradiation. The level of mRNA for γ- glutamylcysteine synthetase was significantly increased at 0.5 h, and remained high until 2 h post-irradiation (50 cGy). The level was transiently lowered to the non-irradiated control level at 3 h and slightly increased again after 6 h post-irradiation. γ-Glutamylcysteine synthetase activity was significantly increased 3 h after irradiation, and remained high up to 24 h post-irradiation. As for glutathione reductase, the mRNA level was increased at 0.5 h, and peaked strongly at 2 h, while the enzyme activity was significantly increased at 6 h after irradiation, and continued to increase up to 24 h. The level of mRNA for thioredoxin, which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked between 0.5 h and 2 h post-irradiation, and rapidly declined thereafter. The content of thioredoxin showed a transient decrease immediately after irradiation, but was then remarkably elevated, reaching a maximum at 3 h, and thereafter declining sharply. These results indicate that the increase in endogenous GSH in mouse brain soon after low-dose γ-ray irradiation is a consequence of the induction of GSH synthesis-related proteins and occurs via both the de novo synthesis and the regeneration pathways.
KW - Glutathione
KW - Low-dose γ-ray
KW - Mouse brain
KW - mRNA for glutathione reductase
UR - http://www.scopus.com/inward/record.url?scp=0032547876&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032547876&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(98)00832-4
DO - 10.1016/S0006-8993(98)00832-4
M3 - Article
C2 - 9767172
AN - SCOPUS:0032547876
VL - 808
SP - 262
EP - 269
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 2
ER -