Evaluation of toxicities of porphyrin derivatives and its possible application

卟啉衍生物的毒性评价及其可能的应用

• 批准号: 13557028
• 负责人: FUJITA Hiroyoshi
• 金额: $ 8.96万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13557028/
• 关键词: metalloporthyrin; heme oxygenase; Bach1; Nrf2; transcriptional control; cell differentiation; erythroid cells; ヘム; NO供与体; ポルフィリン; ヘムオキシゲナーゼ-1; 転写因子; 低酸素応答; 金属; 白血病発症; NFE2; 造血細胞分化

Evaluation of porphyrin derivatives on lives were carried out in the points of effects on cell differentiation as well as on transcription. We, evidenced that Bach1 is the first heme-controlled transcriptional factor in vertebrates. Bach1 is shown to be regulated heme oxygenase-1, which is one of the members of defense system against chemical hazards. Thus, it seems to be possible the evaluation of toxicity via Bach1. In addition, Bach1 also regulates erythroid cell differentiation through globin ge nes. The function of Bach1 can be exchanged by metalloporphyrins other than heme, suggesting some porphyrin derivatives could be applied as drugs to control differentiation.

从对细胞分化和转录的影响两个方面对卟啉衍生物的生命作用进行了评价。我们证明Bach 1是脊椎动物中第一个受血红素调控的转录因子。Bach 1受血红素加氧酶-1（heme oxygenase-1）的调控，是化学危害防御系统的成员之一。因此，似乎可以通过Bach 1评价毒性。此外，Bach 1还通过珠蛋白内斯调控红系细胞分化。Bach 1的功能可以被血红素以外的金属卟啉取代，这表明某些卟啉衍生物可以作为药物来控制分化。

项目成果

N.Nakamura, H.Fujita,.M.Kawata: "Effects of gonadectomy on immunoreactivity for choline acetyltransferase in the cortex, hippocampus, and basal forebrain of adult male rats."Neuroscience. 109. 473-485 (2002)

N.Nakamura、H.Fujita、.M.Kawata：“性腺切除术对成年雄性大鼠皮质、海马和基底前脑中胆碱乙酰转移酶免疫反应性的影响。”神经科学。

K.Kirito, M.Osawa, H.Morita, R.Shimizu, M.Yamamoto, A.Oda, H.Fujita, M.Tanaka, K.Nakajima, Y.Miura, K.Ozawa, N.Komatsu: "A functional role of Stat3 in vivo megakaryopoiesis."Blood. 99. 3220-3227 (2002)

K.Kirito、M.Osawa、H.Morita、R.Shimizu、M.Yamamoto、A.Oda、H.Fujita、M.Tanaka、K.Nakajima、Y.Miura、K.Ozawa、N.Komatsu：“A

K.Ogawa, K.Igarashi, C.Nishitani, S.Shibahara, H.Fujita: "Heme-regulated transcription factor Bach 1."J.Health Sic.(invited review). 48. 1-6 (2002)

K.Okawa、K.Igarashi、C.Nishitani、S.Shibahara、H.Fujita：“血红素调节转录因子 Bach 1”。J.Health Sic.（特邀评论）。

藤田博美: "予防医学事典"朝倉書店、松島綱治、酒井敏行、石川昌、稲寺秀邦(編)(印刷中). (2004)

藤田博美：《预防医学辞典》朝仓书店、松岛纲治、酒井俊之、石川正、稻寺秀国（编）（2004 年出版）。

H. Fujita, et al.: "Regulatory heme and trichloroethylene intoxication : A possible explanation of the case of "A Civil Action""Environ. Health Prevent. Med.. in press. (2002)

H. Fujita 等人：“监管血红素和三氯乙烯中毒：对“民事诉讼”案件的可能解释”Environ。