Localization of glutathione and induction of glutathione synthesis- related proteins in mouse brain by low doses of γ-rays

Shuji Kojima, Osamu Matsuki, Takaharu Nomura, Noriko Shimura, Akiko Kubodera, Kiyonori Yamaoka, Hiroshi Tanooka, Hiro Wakasugi, Yoko Honda, Shuji Honda, Toru Sasaki

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 languageEnglish
Pages (from-to)262-269
Number of pages8
JournalBrain Research
Volume808
Issue number2
DOIs
Publication statusPublished - Oct 19 1998
Externally publishedYes

Fingerprint

Glutathione
Glutamate-Cysteine Ligase
Messenger RNA
Thioredoxins
Brain
Regeneration
Proteins
Oximes
Glutathione Reductase
Autoradiography
Cerebellum
Cysteine
Hippocampus
Enzymes

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 journalArticle

Kojima, S, Matsuki, O, Nomura, T, Shimura, N, Kubodera, A, Yamaoka, K, Tanooka, H, Wakasugi, H, Honda, Y, Honda, S & Sasaki, T 1998, 'Localization of glutathione and induction of glutathione synthesis- related proteins in mouse brain by low doses of γ-rays', Brain Research, vol. 808, no. 2, pp. 262-269. https://doi.org/10.1016/S0006-8993(98)00832-4
Kojima, Shuji ; Matsuki, Osamu ; Nomura, Takaharu ; Shimura, Noriko ; Kubodera, Akiko ; Yamaoka, Kiyonori ; Tanooka, Hiroshi ; Wakasugi, Hiro ; Honda, Yoko ; Honda, Shuji ; Sasaki, Toru. / Localization of glutathione and induction of glutathione synthesis- related proteins in mouse brain by low doses of γ-rays. In: Brain Research. 1998 ; Vol. 808, No. 2. pp. 262-269.
@article{545e9ff2927749ca865fc0bfd84f987c,
title = "Localization of glutathione and induction of glutathione synthesis- related proteins in mouse brain by low doses of γ-rays",
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.",
keywords = "Glutathione, Low-dose γ-ray, Mouse brain, mRNA for glutathione reductase",
author = "Shuji Kojima and Osamu Matsuki and Takaharu Nomura and Noriko Shimura and Akiko Kubodera and Kiyonori Yamaoka and Hiroshi Tanooka and Hiro Wakasugi and Yoko Honda and Shuji Honda and Toru Sasaki",
year = "1998",
month = "10",
day = "19",
doi = "10.1016/S0006-8993(98)00832-4",
language = "English",
volume = "808",
pages = "262--269",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

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 -