2005 Fiscal Year Final Research Report Summary
The study on the regulation of cellular growth and aging process by thioredoxin binding protein
| Project/Area Number |
15209015
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Kyoto University |
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Principal Investigator |
YODOI Junji Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (80108993)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Hajime Kyoto University Hospital, Translational Research Center, Associate Professor, 医学部附属病院, 助教授 (70303914)
MASUTANI Hiroshi Kyoto University, Institute for Virus Research, Associate Professor, ウイルス研究所, 助教授 (50252523)
NABESHIMA Yo-ichi Kyoto University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (60108024)
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| Project Period (FY) |
2003 – 2005
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| Keywords | thioredoxin / thioredoxin binding protein 2 / redox / aging / cancer / Reye syndrome / vitamin D / metabolic syndrome |
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| Research Abstract |
<TBP-2 knockout (KO) mice>
TRX binding protein 2 (TBP-2) binds to reduced TRX but not to oxidized TRX, and is a negative regulator of TRX. We analyzed the function of TBP-2 by means of molecular, cellular approach, and genetically modified mice. TBP-2 KO mice demonstrated increased levels of plasma ketone bodies, pyruvate and lactate, indicating impaired TCA cycle-mediated fatty acid utilization. TBP-2 KO mice share several metabolic features of Reye (-like) syndrome.
<TBP-2 transgenic (TG) mice>
We also produced TBP-2 TG mice and analyzed various phenotypes along with age. TBP-2 TG mice was found to be a mirror image of metabolic phenotype of TBP-2 KO mice, and exhibited characteristic features of precocious aging in their old age.
<The function of TBP-2 in HTLV-1 infected cells>
We found that ectopic overexpression of TBP-2 in HTLV-I-positive T cells resulted in growth suppression along with an increase of p16 and reduction of Rb phosphorylation, suggesting that TBP-2 plays a crucial role in the growth regulation of T cells. The expression of thioredoxin-binding protein-2 (TBP-2) is lost during the transition of HTLV-I-infected T-cell lines. We found that loss of TBP-2 expression was due to DNA methylation and histone deacetylation.
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