The disruption of protein-protein interaction in mitochondria results in sideroblastic anemia.
| Project/Area Number |
15590266
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
FURUYAMA Kazumichi Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (80280874)
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| Co-Investigator(Kenkyū-buntansha) |
HARIGAE Hideo Tohoku University, Hospital, lecture, 病院・講師 (50302146)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | aminolevulinate synthase / succinyl CoA synthethase / hereditary sideroblastic anemia / RNA interference |
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| Research Abstract |
We have identified that beta-subunit of ATP specific succinyl CoA synthase (SCS-betaA) associate with the erythroid specific 5-aminolevulinate synthase (ALAS-E), which is the rate limiting enzyme of heme biosynthetic pathway in erythroid cells. This protein interaction occurred in mitochondria should be important for effective heme production, because succinyl CoA is one of the substrates of ALAS-E for producing aminolevulinic acid. In fact, we have identified that the mutation of the ALAS-E gene, which was identified in the pedigree of pyridoxine refractory X-linked sideroblastic anemia, disrupt this interaction with SCS-betaA, resulting sideroblastic anemia. Since the reduced enzymatic activity of ALAS-E in erythroblast results in X-linked sideroblastic anemia, we have speculated that the disruption of the interaction between ALAS-E and SCS-bataA cause sideroblastic anemia. Thus, we have tried to reduce the expression of SCS-betaA using siRNA technique in erythroid cells. As a result, we found that reduced level of mRNA of SCS-betaA in erythroid cells interfere the erythroid differentiation, which was judged by hemoglobin staining. Our results indicate that the disruption of the association between ALAS-E and SCS-betaA affect the effective heme production in erythroid cells, and it may cause sideroblastic anemia.
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Hypoxemia and blunted hypoxic ventilatory responses in mice lacking heme oxygenase-2.2004
Author(s)
T.Adachi, K.Ishikawa, W.Hida, H.Matsumoto, T.Masuda, F.Date, K.Ogawa, K.Takeda, K.Furuyama, Y.Zhang, T.Kitamuro, H.Ogawa, Y.Maruyama, S.Shibahara
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Journal Title
Biochem Biophys Res Commun. 320
Pages: 514-522
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Bach1 functions as a hypoxia-inducible repressor for the heme oxygenase-1 gene in human cells.2003
Author(s)
T.Kitamuro, K.Takahashi, K.Ogawa, R.Udono-Fujimori, K.Takeda, K.Furuyama, M.Nakayama, J.Sun, H.Fujita, W.Hida, T.Hattori, K.Shirato, K.Igarashi, S.Shibahara
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Journal Title
J Biol Chem. 278
Pages: 9125-9133
Description
「研究成果報告書概要(欧文)」より
Related Report
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