Attenuated repair of radiation-induced DNA damage in primary neural cells from rat embryonic brains - Implication for generation of integration disorder syndrome -
| Project/Area Number |
16591155
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | Nara Medical University |
|---|
Principal Investigator |
KISHIMOTO Toshifumi Nara Medical University, School of Medicine, Professor, 医学部, 教授 (60201456)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Yu Kagawa University, School of Medicine, Professor, 医学部, 教授 (70291440)
YOSHINO Hiroki YOSHINO,Hiroki, 医学部, 助手 (10347560)
MORI Toshio MORI,Toshio, 医学部, 助教授 (10115280)
SUGIURA Shigeki SUGIURA,Shigeki, 医学部, 助教授 (40179130)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | DNA damage / repair / gamma H2AX / radiation / neuron / DSB / astrocyte / double strand break |
|---|
| Research Abstract |
To study the repair of radiation-induced DNA damage in neural cells, primary neurons and astrocytes were prepared in co-culture from 17-day-old rat embryonic brains, and fibroblasts from abdomens of the same embryos were cultured for comparison. Neurons and astrocytes were identified by the staining of MAP2 and GFAP, respectively. Fibroblasts in dishes were irradiated with 0.5-2 Gy of X-rays, fixed, and stained by antibodies against the phosphorylation of histone H2AX (gamma H2AX), since H2AX is rapidly phosphorylated on the induction of DNA double-strand breaks (DSBs) by ionizing radiation. Indeed, X-rays formed various sizes of foci on fibroblasts nuclei, and the number of foci increased in a dose-dependent manner. Interestingly, however, the same doses of X-rays failed to form the gamma H2AX foci on nuclei of neurons and astrocytes. This result suggests that fibroblasts can efficiently repair or respond to X-rays-induced DSBs, while neurons and astrocytes are inefficient. Similar results were observed in the case of nucleotide excision repair, which eliminates helix-distorting DNA damage including UV damage. Neurons and astrocytes repaired less efficiently UV-induced (6-4) photoproducts than fibroblasts, possibly because of low expression of repair protein (PCNA) in neural cells. These results suggest that neurons and astrocytes may be vulnerable to both environmental and intracellular agents, which produce DSBs or helix-distorting DNA damage. Thus, these results have implications for neuronal dysfunction.
|
Report
(3 results)
Research Products
(18 results)
-
-
-
-
-
-
-
-
-
-
[Journal Article] Signal transducer and activator of transcription 3 is a key regulator of keratinocyte survival and proliferation following ultraviolet irradiation.2005
Author(s)
S.Sano, K.S.Chan, M.Kira, K.Kataoka, S.Takagi, M.Tarutani, S.Itami, K.Kiguchi, M.Yokoi, K.Sugasawa, T.Mori, F.Hanaoka, J.Takeda, J.DiGiovanni.
-
Journal Title
Cancer Res. 65
Pages: 5720-5729
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Journal Article] UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiqutin ligase complex.2005
Author(s)
K.Sugasawa, Y.Okuda, M.Saijo, R.Nishi, N.Matsuda, G.Chu, T.Mori, S.Iwai, K.Tanaka, K.Tanaka, F.Hanaoka.
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
-
-
[Journal Article] High prevalence of the hepatitis C virus infection among the inpatients of schizophrenia and psychoactive substance abuse in Japan2004
Author(s)
Naakamura Y, Koh M, Miyoshi E, Ida O, Morikawa M, Tokuyama A, Nagano T, Honda Y, Iida J, Yamamoto K, Minami N, Kasahara A, Hirai M, Hayashi N, Kishimoto T
-
Journal Title
Prog Neuropsychopharmacol Biol Psychiat 28
Pages: 591-597
Related Report
