Increase of Intracellular Glutathione by Low-Dose .GAMMA.-Ray Irradiation Is Mediated by Transcription Factor AP-1 in RAW 264.7 Cells.

Kawakita, Yasunori; Ikekita, Masahiko; Kurozumi, Risa; Kojima, Shuji

doi:10.1248/bpb.26.19

Cited by 38 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These kinases further activate different redox-sensitive transcription factors like Nuclear Factor-kB (NF-kB) and Activating protein-1 (AP-1). The activation of these transcription factors result in the gene expression of various antioxidant defense proteins to overcome the effect of oxidative stress-mediated cellular damage (Kawakita et al 2003). However, our results are in contrast with earlier reports (Yamaoka et al 1991(Yamaoka et al , 1993, which showed a 20 -30% decrease in the lipid peroxidation levels in the rat brain and liver at radiation doses near 50 cGy.…”

Section: Discussioncontrasting

confidence: 99%

“…In the present study, the glutathione level increased significantly (p50.05) at 25 cGy exposure both in lungs and liver suggesting its protective effect in these organs against radiation induced oxidative stress. The increased GSH levels might be due to an increase in the expression of mRNA for g-glutamylcysteine synthetase (g-GCS), a rate limiting enzyme in GSH synthesis , Kawakita et al 2003.…”

Section: Discussionmentioning

confidence: 99%

“…From these reports, it can be postulated that the hormetic/ adaptive response results from an improvement in the levels of reduced glutathione (GSH) and antioxidant enzyme activities in the brain (Kojima et al 1998a(Kojima et al , 1999, spleen (Kojima et al , 2004, liver (Kojima et al 1997(Kojima et al , 1998b(Kojima et al , 1998c, bone marrow and thymus (Yamaoka et al 1991), macrophages (Kawakita et al 2003) and natural killer cells (Kojima et al 2002(Kojima et al , 2004. However, the changes observed were at different radiation doses, dose rates and time intervals using a variety of ionizing radiations.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Low dose gamma-irradiation differentially modulates antioxidant defense in liver and lungs of Balb/c mice

Avti¹,

Pathak²,

Kumar³

et al. 2005

International Journal of Radiation Biology

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Low dose gamma-irradiation differentially modulates antioxidant defense in liver and lungs of Balb/c mice

Avti¹,

Pathak²,

Kumar³

et al. 2005

International Journal of Radiation Biology

View full text Add to dashboard Cite

show abstract

“…The 5 0 -flanking region of the human GCLC gene (L39773) contains a consensus activator protein-1 (AP-1) site and several AP-1-like binding sites, which are also referred to as TRE (PMA-responsive element) or TRE-like elements (Mulcahy and Gipp, 1995;Mulcahy et al, 1997). Several studies suggest that the binding sites in this proximal region are critical to the upregulation of GCL transcription in response to a variety of agents inducing oxidative stress in humans (Sekhar et al, 1997;Rahman et al, 1998;Palomero et al, 2001), as well as other mammals, such as the rat (Yang et al, 2002) and mouse (Kawakita et al, 2003).…”

mentioning

confidence: 99%

Age affects ERK1/2 and NRF2 signaling in the regulation of GCLC expression

Liu

Timblin

et al. 2005

Journal Cellular Physiology

View full text Add to dashboard Cite

We previously reported that activator protein-1 (AP-1) DNA binding activity was increased in vascular smooth muscle cells (VSMC) from old rats when exposed to high glucose or tumor necrosis factor (TNF-a) (Li et al., 2003. J Cell Physiol 197:418-425). We have now examined the relationship between the age-dependent activation of the ERK1/2-AP-1 pathway and modulation of constitutive gene expression of the catalytic subunit of glutamate-cysteine ligase (GCLC) in response to high glucose and TNF-a. GCLC mRNA levels were higher in VSMC from old rats compared to young, a pattern consistent with its protein levels. To determine whether agerelated activation of ERK1/2-AP-1 signaling is responsible for the up-regulation of GCLC, the MEK inhibitors, PD98059 and U0126, were used to block ERK1/2 in VSMC from old rats. An increase in GCLC with inhibitors was observed, diminishing the likelihood of ERK1/2-AP-1 activation as the up-regulating signal for GCLC. However, the transcription factor Nrf2 was higher in nuclei and accompanied by increased Nrf2-ARE binding in VSMC from old rats. Furthermore, MEK inhibitors increased nuclear Nrf2 and Nrf2/ ARE binding. These data suggest opposing effects of Nrf2 and ERK1/2 signaling in the modulation of GCLC expression in old animals.

show abstract

“…Thus, mRNAs for glutathione-synthesis-related proteins in the mouse liver became elevated after low-dose γ -irradiation (Kojima et al, 1998). The low-dose-caused increase in intracellular glutathione in RAW-264.7 cells with its maximum between 3 and 6 hr after exposure was mediated by transcriptional regulation of the γ -glutamylcysteine synthetase gene, predominantly through the AP-1 binding site in its promoter (Kawakita et al, 2003). • Protection against high-dose induced chromosomal aberrations in human lymphocytes increased to a maximum about 4 hr after a conditioning low-dose low-LET irradiation; the protection also operated against other DNA damaging agents (Olivieriet al, 1984;Wolff et al, 1988).…”

Section: Adaptive Protection Responsementioning

confidence: 97%

Responses to Low Doses of Ionizing Radiation in Biological Systems

Feinendegen

Pollycove

Sondhaus

2004

Nonlinearity in Biology, Toxicology, Medicine

View full text Add to dashboard Cite

Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems.To examine tissue effects specific for low-dose radiation, (1) absorbed dose in tissue is replaced by the sum of the energies deposited by each track event, or hit, in a cell-equivalent tissue micromass (1 ng) in all micromasses exposed, that is, by the mean energy delivered by all microdose hits in the exposed micromasses, with cell dose expressing the total energy per micromass from multiple microdoses; and (2) tissue effects are related to cell damage and protective cellular responses per average microdose hit from a given radiation quality for all such hits in the exposed micromasses.The probability of immediate DNA damage per low-linear-energy-transfer (LET) average micro-dose hit is extremely small, increasing over a certain dose range in proportion to the number of hits. Delayed temporary adaptive protection (AP) involves (a) induced detoxification of reactive oxygen species, (b) enhanced rate of DNA repair, (c) induced removal of damaged cells by apoptosis followed by normal cell replacement and by cell differentiation, and (d) stimulated immune response, all with corresponding changes in gene expression. These AP categories may last from less than a day to weeks and be tested by cell responses against renewed irradiation. They operate physiologically against nonradiogenic, largely endogenous DNA damage, which occurs abundantly and continually. Background radiation damage caused by rare microdose hits per micromass is many orders of magnitude less frequent. Except for apoptosis, AP increasingly fails above about 200 mGy of low-LET radiation, corresponding to about 200 microdose hits per exposed micromass. This ratio appears to exceed approximately 1 per day for protracted exposure. The balance between damage and protection favors protection at low cell doses and damage at high cell doses. Bystander effects from high-dosed cells to nonirradiated neighboring cells appear to include both damage and protection.Regarding oncogenesis, a model based on the aforementioned dual response pattern at low doses and dose rates is consistant with the nonlinear reponse data and contradicts the linear no-threshold dose-risk hypothesis for radiation-induced cancer. Indeed, a dose-cancer risk function should include both linear and nonlinear terms.

show abstract

Increase of Intracellular Glutathione by Low-Dose .GAMMA.-Ray Irradiation Is Mediated by Transcription Factor AP-1 in RAW 264.7 Cells.

Cited by 38 publications

References 36 publications

Low dose gamma-irradiation differentially modulates antioxidant defense in liver and lungs of Balb/c mice

Low dose gamma-irradiation differentially modulates antioxidant defense in liver and lungs of Balb/c mice

Age affects ERK1/2 and NRF2 signaling in the regulation of GCLC expression

Responses to Low Doses of Ionizing Radiation in Biological Systems

Contact Info

Product

Resources

About