Development of a novel therapy for brain infarction using a cell-penetrating protein exhibiting enhanced anti-cell death activity
Project/Area Number |
16390257
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Nippon Medical School |
Principal Investigator |
OHTA Shigeo Nippon Medical School, Graduate School of Medicine, Professor (00125832)
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Co-Investigator(Kenkyū-buntansha) |
KATSURA Ken-ichiro Nippon Medical School, Dept. Internal Medicine, Senior Assistant Professor (50297892)
ASOH Sadamitsu Nippon Medical School, Institute of Gerontology, Assistant Professor (70167914)
KAMINURA Naoomi Nippon Medical School, Institute of Gerontology, Assistant Professor (60283800)
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Project Period (FY) |
2004 – 2006
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Project Status |
Completed (Fiscal Year 2006)
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Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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Keywords | mitochondria / PTD-FNK / brain infarction / ischemia / Protein therapy / アポトーシス / 蛋白質導入治療 / Bcl-2ファミリー / 活性酸素 / 虚血・再灌流 / 細胞死 / Bck-xL / 蛋白質導入 |
Research Abstract |
Many practical therapies have been explored for clinical applications to ischemic cerebral infarction; however, the most are still insufficient for treatments for acute stroke. We show here a potential combination therapy in a rat focal ischemic model to improve neurological symptoms as well as reduce infarct volumes at the maximum level. We applied a protein transduction technology using the artificial anti-death FNK protein fused with a protein-transduction-domain peptide (PTD-FNK). When PTD-FNK was administrated at1hr after initiating ischemia followed by the administration of an immunosuppressant FK506 with a 30-min time lag, infarct volumes of the total brain and cortex were markedly reduced to a level of 27% and 14%, respectively. This procedure not only reduced the infarct volume and edema, but also markedly improved neurological symptoms. The therapeutic effect continued at least for 1 week after ischemia. FK506 inhibited the transduction of PTD-FNK in vitro, which explains the requirement of a time lag for the administration of FK506. An additional in vitro experiment showed that PTD-FNK, when administered 30 min before FK506, gave the maximal protective effect through reducing an intracellular calcium concentration. We propose that this combination therapy would give a synergistic protective effect of both drugs, reducing adverse effect of FK506.
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Report
(4 results)
Research Products
(79 results)
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[Journal Article] Transduction of the anti-apoptotic PTD-FNK protein improves the efficiency of transplantation of bone marrow mononuclear cells.2007
Author(s)
Tara, S., Miyamoto, M., Asoh, S, Ishii, N., Yasutake, M., Takagi, G., TAkano, T., Ohta,S.
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Journal Title
J.Mol Cell Cardiol 42・3
Pages: 489-497
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[Journal Article] Protection of hepatic cells from apoptosis induced by ischemia/reperfusion injury by protein therapeutics.2007
Author(s)
Nagai, S., Asoh, S., Kobayashi, Y., Shidara, Y., Mori, T., Suzuki, M., Moriyama, Y., Ohta,S.
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Journal Title
Hepatol.Res. 37・2
Pages: 133-142
NAID
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[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.
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Journal Title
Biochem.Biophys.Res.Commun. (in press)
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[Journal Article] Mitochondrial Genome Variation in Eastern Asia and the Peopling of Japan.2004
Author(s)
Tanaka M, Cabrera VM, Gonzalez AM, Larruga JM, Takeyasu T, Fuku N, Fuo LJ, Hirose R, Fujita Y, Kurata M, Shinoda K, Umetsu K, Yamada Y, Oshida Y, Sato Y, Hattori N, Mizuno Y, Arai Y, Hirose N, Ohta S, Ogawa O, Tanaka Y, Kawamori R, Shamoto-Nagai M, Maruyama W, Shimokata H, Suzuki R, Shimodaira H.
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Journal Title
Genome Res. 14・10A
Pages: 1832-1850
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[Journal Article] Hydrogen acts as a therapeutic anitioxidant by the selective reduction of cytotoxic oxygen radicals.
Author(s)
Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishismaki, K., Yamagata, K., Katsura, K., Katayama, Y., Asoh, S., Ohta,S.
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[Journal Article] Transduction of anti-cell death protein FNK protects isolated rat hearts from myocardial infarction induced by ischemia/reperfusion
Author(s)
Arakawa, M, Yasutake, M., Asoh, S., Miyamoto, M., Takano, T., Ohta,S
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[Journal Article] A Protein Derived From the Fusion of TAT Peptide and FNK,a Bcl-Xl Derivative,prevents Cochlear Hair Cell Death From Aminoglyoside Ototoxicity In Vivo.
Author(s)
Kashio, A., Sakamoto, T., Suzukawa, K., Asoh, S., Ohta, S., Yamasoba,T.
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Journal Title
J.Neurosci,Res. (in press)
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[Book] ミトコンドリアのちから2008
Author(s)
太田成男, 瀬名秀明
Total Pages
423
Publisher
新潮社
Description
「研究成果報告書概要(和文)」より
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