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: 7002217
• 负责人: Svetlana Nikolaevna Radyuk
• 金额: $ 14.21万
• 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 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7002217
• 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.

这项研究的长期目的是了解果蝇果蝇衰老期间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剂酶（过氧蛋白）在调节免疫系统中的作用，并确定该调节与衰老过程的关系。 已知过氧蛋白在保护细胞免受氧化损伤的状态非常重要，最近的研究结果表明它们也参与了免疫系统的调节。 拟议研究的实验策略将是通过操纵过氧蛋白表达的水平来确定个体过氧蛋白基因的功能意义。通过RNA干扰和/或使用标准遗传方法获得的突变等位基因，将通过RNA干扰和/或使用过氧蛋白基因表达的抑制作用。通过转基因方法学可以增强过氧化物活性。过氧毒素表达对抗菌肽诱导性和果蝇对感染的敏感性的影响将使用分子，生物学和细菌学技术确定。此外，通过过氧蛋白对免疫系统的调节将作为年龄的函数评估。 这项研究的结果将i）直接测试过氧蛋白基因在先天免疫中的作用，ii）允许评估先天免疫和衰老之间的相互关系。这将为对衰老期间先天免疫的分子基础进行更全面的研究奠定了基础。

项目成果

Peroxiredoxin 5 modulates immune response in Drosophila.

• DOI: 10.1016/j.bbagen.2010.06.010
• 发表时间: 2010-11
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
• 影响因子: 3
• 作者: Radyuk, Svetlana N.;Michalak, Katarzyna;Klichko, Vladimir I.;Benes, Judith;Orr, William C.
• 通讯作者: Orr, William C.