2007 Fiscal Year Final Research Report Summary
Research for requirement of down-regulation of energy metabolism for neuronal differentiation
| Project/Area Number |
17500263
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | Nippon Medical School |
|---|
Principal Investigator |
OHSAWA Ikuroh Nippon Medical School, Institute of Gerontology, Senior Assistant Professor (30343586)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAMIMURA Naomi Nippon Medical School, Assistant Professor (60283800)
OHTA Shigeo Nippon Medical School, Graduate School of Medicine, Professor (00125832)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Keywords | Neuroscience / Differentiation / Mitochondria / Brain / Signal transduction |
|---|
| Research Abstract |
Only a few human neuroblastoma cell-lines maintain the potential for neuronal differentiation. We noticed by chance that differentiable human neuroblastomas including SH-SY5Y have a specific mutation in the dihydrolipoamide-succinyltransferase (DLST) gene, whose product is a component of the α-ketoglutarate-dehydrogenase complex involved in mitochondrial energy metabolism. Here we demonstrate a requirement of energy-reduction for neuronal differentiation by restoring SH-SY5Y with the wild-type DLSTgene. Up-regulation of DLST activity increased mitochondrial membrane potential and impaired neuronal differentiation. The impairment was partially rescued by treatment with inhibitors of energy metabolism. Additionally, down-regulation of DLST expression with small interfering RNA enhanced neuronal differentiation in rat pheochromocytoma PC12 and primary cultured neocortical cells. We further found that mitochondrial membrane potential among SH-SY5Y cells was heterogeneous and lower in neuroblastic type cells. It is thus concluded that the casual mutation conferred the potential for differentiation on the neuroblastomas, suggesting that such mutants had been preferentially selected as a model cell-line for neuronal differentiation. The energy-reduction seemed to contribute to the differentiation by preventing cell-death. These results provide a new insight into neuronal differentiation.
|
Research Products
(42 results)
-
-
-
[Journal Article] 加齢2008
Author(s)
大澤 郁朗
-
Journal Title
アルツハイマー病-基礎研究から予防・治療の新しいパラダイム-日本臨牀増刊 66(増刊)1
Pages: 169-174
Description
「研究成果報告書概要(和文)」より
-
-
[Journal Article] Combination therapy with transductive anti-death FNK protein and FK506 ameliorates brain damage with focal transient ischemia in rat2008
Author(s)
Katsura, KI., Takahashi, K., Asoh, S., Watanabe, M., Sakurazawa, M., Ohsawa, I., Mod, T., Igarashi, H., Ohkubo, S., Katayama, Y., Ohta, S
-
Journal Title
J. Neurochem doi : 10.1111/j.0022-3042.2008.05360.x
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Journal Article] Glioma patient prognosis by combined immunostaining for survivin, Ki-67 and epidermal growth factor receptor2007
Author(s)
Kogiku, M., Ohsawa, I., Matsumoto, K., Sugisaki, Y., Takahashi, H., Teramoto, A., Ohta, S
-
Journal Title
J. Clin. Neurosci. doi : 10.1016/j.jocn.2007.11.012
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Journal Article] Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals.2007
Author(s)
Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., Katsura, Katayama, Y., Asoh, S., Ohta, S
-
Journal Title
Nat. Med 13
Pages: 688-694
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Prognostic significance of the immunohistchemical index of surviving in glioma : A comparative study with the MIB-1 index.2005
Author(s)
Uematsu, M., Ohsawa, I., Aokage, T., Nishimaki, K., Matsumoto, K., Takahashi H., Asoh, S., Teramoto A, Ohta S
-
Journal Title
J. Neuro-Oncology 72
Pages: 231-238
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] The anti-cell death FNK protein protects cells from death induced by freezing and thawing.2005
Author(s)
Sudo, K., Asoh, S., Ohsawa, I., Ozaki, D., Yamagata, K., Ito, H., Ohta, S
-
Journal Title
Biochem. Biophys. Res. Commun 330
Pages: 850-856
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Presentation] Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals in the nervous system.2007
Author(s)
Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., Katsura,K.-I., Asoh, S., Ohta, S
Organizer
IPA 2007 Osaka Silver Congress
Place of Presentation
Osaka Japan
Year and Date
20071000
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Presentation] Role of Mitochondrial aldehyde dehydrogenase in the onset of Alzheimer's Disease2006
Author(s)
Ohsawa, I., Nishimaki, K., Murakami, Y., Suzuki, Y., Ishikawa, M., Ohta, S
Organizer
The 10th International Conference on Alzheimer's Disease and Related Disorders
Place of Presentation
Madrid Spain
Year and Date
20060700
Description
「研究成果報告書概要(欧文)」より
-
[Presentation] Neurodegeneration in mice expressing a dominant negative form of mitochondrial aldehyde dehydrogenase.2006
Author(s)
Ohsawa, I., Nishimaki, K., Murakami, Y., Suzuki, Y., Ishikawa, M., Ohta, S
Organizer
20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress
Place of Presentation
Kyoto Japan
Year and Date
20060600
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Presentation] Deficiency in a mitochondrial aldehyde dehydrogenase promotes oxidative stress and the onset of Alzheimer's disease : Its molecular mechanisms and animal models2005
Author(s)
Ohsawa, I., Nishimaki, K., Murakami, Y., Suzuki, Y., Ishikawa, M., Ohta, S
Organizer
International Conference on Mitochondria and Life 2005
Place of Presentation
Tokyo Japan
Year and Date
20051200
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
