Elucidating in vivo functions of hydrogen peroxide

阐明过氧化氢的体内功能

• 批准号: RGPIN-2019-06766
• 负责人: Hurd, Thomas
• 金额: $ 2.99万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688238
• 关键词: Elucidating; vivo; functions; hydrogen; peroxide

Essential to an organism's survival is its ability to restore and maintain tissue integrity following injury. One of the earliest and most crucial responses to injury is the production of the oxidant hydrogen peroxide (H2O2). It is often the case that free radicals and oxidants, such as H2O2, are harmful and toxic; however, under certain circumstances, such as injury, cells in our bodies generate oxidants for beneficial purposes, for example to repair damage and heal. Using genetic and biochemical approaches, the central objective of this research proposal is to uncover how H2O2 helps to restore tissue integrity upon injury and damage. ******Our first aim is to determine what triggers the generation of H2O2 upon injury. Cells have special type of enzymes they use to generate H2O2 in response to injury; however, how they know when to activate these enzymes remains unknown. Using powerful genetic approaches in the model organism, the fruit fly, we will determine how cells turn on this enzyme during injury. ******Our second aim is to understand how, once produced, H2O2 helps to restore and repair injury. A main proposed function for injury-induced H2O2 is to alert immune cells that injury has occurred and to attract them to the site of injury. Once at the site of injury, immune cells are essential to stave off infection and repair damage. How H2O2 alerts and attracts immune cells remains unknown. Using both genetic and biochemical approaches we will elucidate this critical and essential function of H2O2 in injury repair. ******Our research will beneficially impact Canadians in numerous ways, including by training highly qualified personnel, by developing Canada's research capacity, and through scientific knowledge advancement. This research program will elevate Canada as a hub for research innovation and excellence in the basic biomedical sciences and redox biology. In doing so it will stimulate economic and societal growth through the training and recruitment of world-class scientists. **

生物体的生存至关重要的是它在损伤后恢复和保持组织完整性的能力。对损伤最早和最关键的反应之一是产生氧化剂过氧化氢（H2O2）。通常情况下，自由基和氧化剂，如H2O2，是有害的，有毒的；然而，在某些情况下，比如受伤，我们体内的细胞会产生有益的氧化剂，比如修复损伤和愈合。利用遗传和生化方法，本研究计划的中心目标是揭示H2O2如何帮助恢复损伤和损伤后的组织完整性。******我们的第一个目标是确定是什么触发了H2O2的产生。细胞有一种特殊的酶，用来产生H2O2以应对损伤；然而，他们如何知道何时激活这些酶仍然未知。使用强大的遗传方法在模式生物果蝇中，我们将确定细胞在受伤时如何激活这种酶。******我们的第二个目标是了解一旦产生H2O2是如何帮助恢复和修复损伤的。损伤诱导的H2O2的一个主要功能是提醒免疫细胞损伤已经发生，并将它们吸引到损伤部位。一旦到达受伤部位，免疫细胞对避免感染和修复损伤至关重要。H2O2如何提醒和吸引免疫细胞仍然未知。利用遗传和生化方法，我们将阐明H2O2在损伤修复中的关键和基本功能。******我们的研究将在许多方面对加拿大人产生有益的影响，包括通过培训高素质的人才，通过发展加拿大的研究能力，以及通过科学知识的进步。该研究项目将使加拿大成为基础生物医学和氧化还原生物学研究创新和卓越的中心。在这样做的过程中，它将通过培训和招聘世界级科学家来刺激经济和社会增长。**