The Role of Iron and Nitric Oxide on Inflammation and Carcinogenesis

铁和一氧化氮在炎症和癌变中的作用

• 批准号: 09670227
• 负责人: KAWABATA Teruyuki
• 金额: $ 1.73万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670227/
• 关键词: inflammation; carcinogenesis; iron; nitric oxide

We studied changes of iron metabolism on inflammation and the role of iron concerning with nitric oxide generation. We prepared iron-loaded rats fed with 2.5% carbonyl iron and induced inflammation by a single I.p. injection of lipopolysaccharide (LPS) into the rats. The iron overload was checked with histochemical and biochemical studies. In this model, serum AST and ALT did not increase significantly and were not different between iron-loaded and control rats. Serum iron decreased transiently after LPS injection and the decrease was less intensive in iron-loaded rats than control. Inducible nitric oxide synthase (iNOS) was induced at an early stage on several organs and disappeared until 24 and 48 hours. However, serum nitrogen oxides (NOx) and nitrosyl hemoglobin (NO-Hb) were kept high even after the disappearance of iNOS. We did not find the significant differences of several free radical damage such as protein oxidation, but the necrotic foci and the death rate appeared different between iron-loaded and control rats. In vitro study of the effect of nitric oxide on aconitase, which is a family protein of iron-regulatory protein-1 (IRP-1), nitric oxide inactivated the aconitase under atmosphere, but could not detect thyl radical which has been reported. In model iron-complex of hydroxylipoic acid and hydroxylipoamide, we did not detect thyl radical. The chemical mechanism of nitric oxide on aconitase inactivation was still unclear. It may need another methodological approach.

我们研究了铁代谢对炎症的变化以及一氧化氮产生的铁的作用。我们制备了富含2.5％羰基铁的铁的大鼠，并诱导了单腹腔炎。将脂多糖（LPS）注入大鼠。通过组织化学和生化研究检查了铁超负荷。在该模型中，血清AST和ALT并未显着增加，并且在铁压和对照大鼠之间没有差异。 LPS注射后血清铁瞬时降低，而在铁负载的大鼠中的降低不如对照。在几个器官的早期阶段诱导诱导型一氧化氮合酶（INOS），直到24和48小时消失。然而，即使在iNOS消失后，血清氮氧化物（NOX）和亚硝基血红蛋白（NO-HB）也保持较高。我们没有发现几种自由基损伤（例如蛋白质氧化）的显着差异，但是坏死灶和死亡率在载荷大鼠和对照大鼠之间似乎有所不同。一氧化氮对刺激酶的作用的体外研究，粘结酶是铁调节蛋白-1（IRP-1）的家族蛋白，一氧化氮在大气下灭活了刺刺酶，但无法检测到据报道的硫基自由基。在模型的羟基酰亚酸和羟基酰胺的铁复合物中，我们没有检测到囊体自由基。一氧化氮在抗衰素失活上的化学机制尚不清楚。它可能需要另一种方法论方法。

项目成果

Ma, Y., Kawabata, T., Hamazaki, S., Ogino, T., and Okada, S.: "Sex differences in oxidative damage in ddY mouse kidney treated with a renal carcinogen, iron nitrilotriacetate"Carcinogenesis. 19・11. 1983-1988 (1998)

Ma, Y.、Kawabata, T.、Hamazaki, S.、Ogino, T. 和 Okada, S.：“用肾癌物质次氮基三乙酸铁治疗的 ddY 小鼠肾脏氧化损伤的性别差异”致癌作用 19・11。 .1983-1988 (1998)

Ma, Y., Xian, M., Li, J., Kawabata, T. and Okada, S.: "Interrelations of clinicopathological variables, local immune response and prognosis in esophageal squamous cell carcinoma"APMIS. 107(5). 514-522 (1999)

Ma，Y.，Xian，M.，Li，J.，Kawabata，T.和Okada，S.：“食管鳞状细胞癌临床病理变量、局部免疫反应和预后的相互关系”APMIS。

Ma, Y.: "Cupric nitrilotriacetate-induced apoptosis in HL-60 cells association with lipid peroxidation, release of cytochrome C from mitochondria, and activation of caspase-3"Free Radical Biology & Medicine. 27・1-2. 227-233 (1999)

Ma, Y.：“次氮基三乙酸铜诱导的 HL-60 细胞凋亡与脂质过氧化、线粒体中细胞色素 C 的释放以及 caspase-3 的激活有关”自由基生物学与医学 27・1-233。 (1999)

Kawabata, T., Ma, Y., Yamadori, I. and Okada, S.: "Iron-induced apoptosis in mouse renal proximal tubules after an injection of a renal carcinogen, iron-nitrilotriacetate"Carcinogenesis. 18・7. 1389-1394 (1997)

Kawabata, T.、Ma, Y.、Yamadori, I. 和 Okada, S.：“注射肾致癌物次氮基三乙酸铁后铁诱导的小鼠肾近端小管细胞凋亡”18・7。 1394 (1997)

Ma, Y., Cao L., Kawabata, T., Yoshino, T., Yang B.B. and Okada, S.: "Cupric nitrilotriacetate induces oxidative DNA damage and apoptosis in human leukemia HL-60 cells"Free Radical Biology & Medicine. 25・4-5. 568-575 (1998)

Ma, Y.、Cao L.、Kawabata, T.、Yoshino, T.、Yang B.B. 和 Okada, S.：“次氮基三乙酸铜诱导人白血病 HL-60 细胞中的氧化性 DNA 损伤和细胞凋亡”自由基生物学与医学。 25・4-5。568-575（1998）