title: Activation of de novo GSH synthesis pathway in mouse spleen after long term low-dose γ-ray irradiation.
abstract: Glutathione (GSH) is an important cellular antioxidant and has a critical role in maintaining the balance of cellular redox. In this study, we investigated the GSH biosynthesis genes involved in the elevation of endogenous GSH levels using an irradiation system with an irradiation dose rate of 1.78 mGy/h, which was about 40,000 times less than the dose rates used in other studies. The results showed that GSH levels were significantly increased in the low-dose (0.02 and 0.2 Gy) irradiated group compared to those in the non-irradiated group, but enzymatic antioxidants such as superoxide dismutase and catalase were not induced at any doses tested. The elevation in GSH was accompanied by elevated expression of glutamate-cysteine ligase modifier subunit, but no changes were observed in the expression of glutamate-cysteine ligase catalytic subunit and thioredoxin in de novo GSH synthesis. In the case of genes involved in the GSH regeneration cycle, the expression of glutathione reductase was not changed after irradiation, whereas glutathione peroxidase was only increased in the 0.2 Gy irradiated group. Collectively, our results suggest that the de novo pathway, rather than the regeneration cycle, may be mainly switched on in response to stimulation with long-term low-dose radiation in the spleen.
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Science , 40 Jwadong-gil, Jangan-eup, Gijang-gun, Busan, Republic of Korea.
authors.forename: E K
authors.initials: EK
authors.lastname: Lee
authors.forename: J A
authors.initials: JA
authors.lastname: Kim
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.forename: S J
authors.initials: SJ
authors.lastname: Park
authors.forename: K
authors.initials: K
authors.lastname: Heo
authors.forename: K M
authors.initials: KM
authors.lastname: Yang
authors.forename: T G
authors.initials: TG
authors.lastname: Son
mesh_terms: D000818:Animals; D002374:Catalase / Q000528:radiation effects; D005720:Gamma Rays; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis* / Q000235:genetics / Q000528:radiation effects; D005978:Glutathione / Q000096:biosynthesis* / Q000378:metabolism / Q000528:radiation effects*; D005979:Glutathione Peroxidase / Q000528:radiation effects; D005980:Glutathione Reductase / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000378:metabolism / Q000528:radiation effects*; D013482:Superoxide Dismutase / Q000528:radiation effects; D013879:Thioredoxins
chemical_list: D012333:RNA, Messenger; D013879:Thioredoxins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; C560749:GCLM protein, mouse; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione