Effect of Oxidative and Nitroxidative stress on Bacterial survival under various oxygen tension

氧化和硝基氧化应激对不同氧张力下细菌存活的影响

• 批准号: 14570127
• 负责人: SATO Eisuke
• 金额: $ 2.24万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570127/
• 关键词: Reactive Oxyge Species; nitric oxide; Bacteria; Mutation; NADH oxidase; Nitirite reductase; 遺伝子進化; 持続感染; 微生物; 酵素環境; 遺伝子変異

Despite the presence of bactericidal factors and activated neutrophils in saliva and the oral cavity, large numbers of bacteria including S.mutans are living in the oral cavity of human subjects. Because oral concentrations of NO and related metabolites are fairly high, we examined the effect of NO and related compounds on the metabolism of E.coli and S.mutans. Unlike E.coli, S.mutans metabolizes molecular oxygen to H_2O_2 and then to H_2O by using two types of NADH oxidases (Nox-1 and 2). Kinetic analysis using chemiluminescence and electron paramagnetic resonance methods revealed that the wild-type but not knock out species of S.mutans lacking Nox-1, 2 and AhpC generated the superoxide radical via Nox-1-dependent pathway. Although NO did not appreciably affect the oxygen consumption by S.mutans, it increased cellular levels of immunoreactive nitrotyrosyl proteins and inhibited their proliferation particularly under low oxygen tensions. Under air atmospheric conditions, however, NO failed to inhibit the proliferation of S.mutans. Moreover, S.mutans was found to generate NO from nitrite. These results indicate that generation of superoxide and NO is critically important for the survival of S.mutans in the oral cavity enriched with bactericidal metabolites and activated neutrophils.

尽管唾液和口腔中存在杀菌因子和激活的中性粒细胞，但包括变形链球菌在内的大量细菌仍生活在人体口腔中。由于口服NO及相关代谢物的浓度相当高，因此我们研究了NO及相关化合物对大肠杆菌和变形链球菌代谢的影响。与大肠杆菌不同，变形链球菌通过两种类型的NADH氧化酶(NOX-1和NADH-2)将分子氧代谢成H_2O_2，然后再代谢成H_2O。化学发光和电子顺磁共振的动力学分析表明，缺乏NOx-1、2和AhpC的野生型但未敲除的变形链球菌通过依赖于NOx-1的途径产生超氧阴离子自由基。虽然NO对变形链球菌的耗氧量没有明显的影响，但它增加了细胞内免疫反应的硝基酪氨酰蛋白的水平，并抑制了它们的增殖，特别是在低氧压下。然而，在大气条件下，NO未能抑制变形链球菌的增殖。此外，还发现变形链球菌能从亚硝酸盐中产生NO。这些结果表明，超氧化物和NO的产生对口腔中富含杀菌代谢产物和激活的中性粒细胞的变形链球菌的生存至关重要。

项目成果

AM Park, K Nagata.EF Sato, T Tamura, M Inoue: "Different sensitvity to nitric oxide in Helicobactor pylori and Eschelichia coli is due to the subtype of cytochrome c oxidase"Aech.Biochem.Biophys.. 411(1). 129-135 (2003)

AM Park、K Nagata.EF Sato、T Tamura、M Inoue：“幽门螺杆菌和大肠杆菌对一氧化氮的敏感性不同是由于细胞色素 C 氧化酶的亚型所致”Aech.Biochem.Biophys.. 411(1)。

Chang BJ, Nishikawa M, Sato EF, Inoue M: "Mice lacking inducible nitric oxide synthase show strong resistance to anti-Fas antibody-induced fulminant hepatitis"Arch.Biochem.Biophys.. 411. 63-72 (2003)

Chang BJ、Nishikawa M、Sato EF、Inoue M：“缺乏诱导型一氧化氮合酶的小鼠对抗 Fas 抗体诱导的暴发性肝炎表现出强大的抵抗力”Arch.Biochem.Biophys.. 411. 63-72 (2003)

Sato, E.F., Higashino, M., Ikeda, K., Wake, R., Matsuo, M., Utsumi, K.: "Oxidative stress-induced cell death in oral neutrophils"Am.J.Phyiol.-Cell Physiol.. 28. C1048-C1053 (2003)

Sato, E.F.、Higashino, M.、Ikeda, K.、Wake, R.、Matsuo, M.、Utsumi, K.：“口腔中性粒细胞中氧化应激诱导的细胞死亡”Am.J.Phyiol.-Cell Physiol。

S.L.Nuttall, H.C.Routledge, S.Manney, M.Tsuchiya, A.Asada, M.Shindo, E.Kasahara, EF.Sato, M.Inoue: "Circulating and Exhaled Markers of Nitric Oxide and Antioxidant Activity After Smoking Response"Circulation. 106. 145e-146e (2002)

S.L.Nuttall、H.C.Routledge、S.Manney、M.Tsuchiya、A.Asada、M.Shindo、E.Kasahara、EF.Sato、M.Inoue：“吸烟反应后一氧化氮和抗氧化活性的循环和呼出标记物”循环

Okai Y, Sato EF, Okai, Inoue M: "Effect of endocrine disruptor para-nonylphenol on the cell growth and oxygen radical generation in esherichia coli mutant cells deficient in catalase and superoxide dimutase"Free Radical biology & Medicine. (in press). (20

Okai Y、Sato EF、Okai、Inoue M：“内分泌干扰物对壬基酚对缺乏过氧化氢酶和超氧化物歧化酶的大肠杆菌突变细胞中细胞生长和氧自由基产生的影响”自由基生物学