2013 Fiscal Year Final Research Report
Development of therapeutic agents for ischemia/reperfusion injury utilizing a novel regulatory mechanism of Parp1
| Project/Area Number |
23790201
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
OKITA Naoyuki 東京理科大学, 薬学部, 助教 (60453841)
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| Project Period (FY) |
2011 – 2013
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| Keywords | PARP1 / Nutlin3a / Caylin2 / 虚血再灌流障害 / p53 / プロテアソーム |
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| Research Abstract |
PARP1 is an important enzyme involved in various patho-physiological phenomena such as ischemia/reperfusion (I/R) injury, which occurs when blood flow is restored after cerebral infarction, myocardial infarction and transplantation of various organs. I/R-induced PARP1 over-activation is mediated by production of reactive oxygen species and is involved in NF-κB transactivation. For these reasons, PARP1 is an attractive target for strategies to protect against I/R injury. Because we found that Nutlin-3a, an MDM2 inhibitor, treatment reduces the protein levels of PARP1 in culture cells, we investigated the novel regulatorymechanism of PARP1 for development of therapeutic agents for ischemia/reperfusion injury. Consequently we obtained the results that Nutlin-3a and its analogue Caylin-2 treatment induce proteasomal degradation of PARP1 in a p53-dependent manner, and the down-regulation of PARP1 is reversible and accompanied with an inflammatory response. For protection against I/R injury, our results support the usability of the p53 inducible cis-imidazoline compounds, Nutlin-3a and its analogs, as PARP1 inhibitors.
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[Journal Article] Caloric restriction-associated remodeling of rat white adipose tissue: Effects on the growth hormone/insulin-like growth factor-1 axis2012
Author(s)
Chujo Y, Fujii N, Okita N (Co-1st author), Konishi T, Narita T, Yamada A, Haruyama Y, Tashiro K, Chiba T, Shimokawa I, Higami Y
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Journal Title
sterol regulatory element binding protein-1 and macrophage infiltration
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[Journal Article] Differential Responses of White Adipose Tissue and Brown Adipose Tissue to Caloric Restriction in Rats2012
Author(s)
Okita N, Hayashida Y, Kojima Y, Fukushima M, Yuguchi K, Mikami K, Yamauchi A, Watanabe K, Noguchi M, Nakamura M, Toda T, Higami Y
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Journal Title
Mechanisms of Ageing and Development
Volume: 133
Pages: 255-266
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