The Role of Peroxiredoxins in Immunity and Aging

过氧化还原蛋白在免疫和衰老中的作用

• 批准号: 6849375
• 负责人: Svetlana Nikolaevna Radyuk
• 金额: $ 17.81万
• 依托单位: SOUTHERN METHODIST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849375
• 关键词: Drosophilidae; RNA interference; age difference; aging; arthropod genetics; gene expression; humoral immunity; immune response; immunity; immunosenescence; mutant; peroxidases; redoxin; respiratory protein

The long-term objective of this research is to understand the molecular mechanisms governing the regulation of innate immunity during aging in Drosophila melanogaster. More specifically, the proposed study will determine the role of a family of recently discovered antioxidant enzymes - peroxiredoxins - in regulating the immune system and to determine how this regulation relates to the aging process. Peroxiredoxins are known to be important in protecting cells against oxidative insult and the results of recent studies indicate that they are also involved in modulation of the immune system. The experimental strategy for the proposed research will be to determine the functional significance of individual peroxiredoxin genes primarily by manipulating the levels of peroxiredoxin expression. The inhibition of peroxiredoxin gene expression will be achieved by RNA interference and/or through the use of mutant alleles obtained by standard genetic approaches. Enhancement of peroxiredoxin activity will be achieved by transgenic methodology. The effects of the expression of peroxiredoxins on the inducibility of antimicrobial peptides and sensitivity of Drosophila to infection will be determined using molecular, biological, and bacteriological techniques. In addition, regulation of the immune system by peroxiredoxins will be assessed as a function of age. The results of this study will i) provide a direct test of the role of peroxiredoxin genes in innate immunity, and ii) permit the assessment of the interrelationship between the regulation of innate immunity and aging. This will set the stage for a more thorough investigation of the molecular underpinnings of innate immunity during aging.

这项研究的长期目标是了解果蝇衰老过程中先天免疫调节的分子机制。更具体地说，拟议的研究将确定最近发现的抗氧化酶家族（过氧化还原酶）在调节免疫系统中的作用，并确定这种调节与衰老过程的关系。 众所周知，过氧化还原蛋白对于保护细胞免受氧化损伤很重要，最近的研究结果表明它们还参与免疫系统的调节。 拟议研究的实验策略将是主要通过操纵过氧化还原蛋白表达水平来确定单个过氧化还原蛋白基因的功能意义。过氧化还原蛋白基因表达的抑制将通过RNA干扰和/或通过使用通过标准遗传方法获得的突变等位基因来实现。过氧化还原蛋白活性的增强将通过转基因方法来实现。将使用分子、生物学和细菌学技术来确定过氧化还原蛋白的表达对抗菌肽的诱导性和果蝇对感染的敏感性的影响。此外，过氧化还原蛋白对免疫系统的调节将作为年龄的函数进行评估。 这项研究的结果将 i) 提供过氧化还原蛋白基因在先天免疫中的作用的直接测试，以及 ii) 允许评估先天免疫调节与衰老之间的相互关系。这将为更彻底地研究衰老过程中先天免疫的分子基础奠定基础。