Radyuk Svetlana N, Michalak Katarzyna, Klichko Vladimir I, Benes Judith, Rebrin Igor, Sohal Rajindar S, Orr William C
Department of Biological Sciences, Southern Methodist University, 6501 Airline Rd., Dallas, TX 75275, USA.
Biochem J. 2009 Apr 15;419(2):437-45. doi: 10.1042/BJ20082003.
Peroxiredoxin 5 is a distinct isoform of the peroxiredoxin gene family. The antioxidative and anti-apoptotic functions of peroxiredoxin 5 have been extensively demonstrated in cell culture experiments. In the present paper, we provide the first functional analysis of peroxiredoxin 5 in a multicellular organism, Drosophila melanogaster. Similar to its mammalian, yeast or human counterparts, dPrx5 (Drosophila peroxiredoxin 5) is expressed in several cellular compartments, including the cytosol, nucleus and the mitochondrion. Global overexpression of dPrx5 in flies increased resistance to oxidative stress and extended their life span by up to 30% under normal conditions. The dprx5(-/-) null flies were comparatively more susceptible to oxidative stress, had higher incidence of apoptosis, and a shortened life span. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) analysis revealed that the dprx5(-/-) null mutant had discernible tissue-specific apoptotic patterns, similar to those observed in control flies exposed to paraquat. In addition, apoptosis was particularly notable in oenocytes. During development the dPrx5 levels co-varied with ecdysone pulses, suggesting inter-relationship between ecdystreroids and dPrx5 expression. The importance of dPrx5 for development was further underscored by the embryonic lethal phenotype of progeny derived from the dprx5(-/-) null mutant. Results from the present study suggest that the antioxidant and anti-apoptotic activities of dPrx5 play a critical role in development and aging of the fly.
过氧化物酶体增殖物激活受体5是过氧化物酶体增殖物激活受体基因家族的一个独特亚型。过氧化物酶体增殖物激活受体5的抗氧化和抗凋亡功能已在细胞培养实验中得到广泛证实。在本文中，我们首次在多细胞生物黑腹果蝇中对过氧化物酶体增殖物激活受体5进行了功能分析。与它的哺乳动物、酵母或人类对应物相似，dPrx5（果蝇过氧化物酶体增殖物激活受体5）在几个细胞区室中表达，包括细胞质、细胞核和线粒体。在果蝇中全局过表达dPrx5可增加对氧化应激的抗性，并在正常条件下使其寿命延长多达30%。dprx5(-/-)基因敲除果蝇对氧化应激相对更敏感，凋亡发生率更高，寿命缩短。TUNEL（末端脱氧核苷酸转移酶介导的dUTP缺口末端标记）分析显示，dprx5(-/-)基因敲除突变体具有明显的组织特异性凋亡模式，类似于在接触百草枯的对照果蝇中观察到的模式。此外，凋亡在oenocytes中尤为明显。在发育过程中，dPrx5水平与蜕皮激素脉冲共同变化，表明蜕皮类固醇与dPrx5表达之间存在相互关系。dPrx5对发育的重要性进一步体现在dprx5(-/-)基因敲除突变体后代的胚胎致死表型上。本研究结果表明，dPrx5的抗氧化和抗凋亡活性在果蝇的发育和衰老中起关键作用。
