| Project/Area Number |
07044217
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
FUJITA Hiroyoshi Tohoku Univ., Assoc.Prof., 医学部, 助教授 (60142931)
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| Co-Investigator(Kenkyū-buntansha) |
SASSA Shigeru The Rockefeller Univ., Head of Lab., 血液生化学, 研究室長
ROMEO PaulーH INSERM, 血液分子遺伝学, 部長
ENCEL James ノースウェスターン大学, 生化学・分子生物学, 教授
AKAGI Reiko Okayama Prefect.Univ., Assoc.Prof., 保健福祉学部, 助教授 (50150967)
YAMAMOTO Masayuki Tsukuba Univ., Prof., 基礎医学系, 教授 (50166823)
ENGEL James Douglas Northwestern Univ., Prof.
ROMEO Poul Henri INSERM,Director
ENGEL James. ノースウェスターン大学, 生化学・分子生物学, 教授
ENGEL James ノースウエスタン大学, 生化学・分子生物学, 教授
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥11,300,000 (Direct Cost: ¥11,300,000)
Fiscal Year 1997: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1996: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1995: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | delta-Aminolevulinate synthase / erythroid transcription factor / heme bicsynthesis / globin biosynthesis / NF-E2 / p18 / ヘム / 赤血球分化 / 鉄芽球系貧血 / ヘム代謝 / δ-アミルブリン酸合成酵素 / 先天性ヘム代謝障害 |
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| Research Abstract |
We have investigated the special roles of erythroid type transcription factors, such as GATA-1 and NF-E2, on erythroid cell differentiation with special reference to heme biosynthesis. When expressions of erythroid specific delta-Aminolevulinate synthase (ALAS-E) in mouse erythroleukemia (MEL) cells was disturbed by anti-sense technique, expressions of every enzymes for heme biosynthesis pathway decreaded possibly due to decline in NF-E2 (Meguro et al., 1996) . This ovservation is in good agreement with previous results in DMSO-resistant clone of MEL cells (Fujita et al., 1991) .
Then, we constructed ES cells lacking ALAS-E gene. The cells expressed almost same amount of GATA-1 and NF-E2 when compared with wild type cells. The cells, however, cannot accumulate heme, benzidine positive cells, and beta-major globin mRNAs after undergoing erythroid differentiation (Haigae et al., 1998) . Thus, it is obvious that ALAS-E mediated heme biosynthesis regulates erythroid differentiation not only through transcription activity of NF-E2 (Nagai et al, 1998) but also through mature type globin synthesis during late stage of erythroid differentiation.
It is also demonstrated that mice lacking p18 subunit of NF-E2 was lethal. Using testis specific promoter, GATA-1 knock down mice was also obtained. The knock down mice was also lethal, however, analyzes of fetus indicated a marked decline in hemoglobinized cells.
As far as we examined nonspecific delta-aminolevulinate synthase (ALAS-N), the gene was negatively regulated via NF-KB binding sequence (Fujita, 1998) .
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