Cooperative action of antioxidant defense systems in Drosophila
Cooperative action of antioxidant defense systems in Drosophila
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DOI：
10.1016/s0960-9822(01)00393-1
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发表时间：
2001-08-21
期刊：
影响因子：
9.2
通讯作者：
Jäckle, H
中科院分区：
文献类型：
--
作者：
Missirlis, F;Phillips, JP;Jäckle, H
分子氧是有氧生活的关键，但也转化为细胞毒性副产物，称为活性氧（ROS）[1]。保护细胞免受ROS诱导的损伤的细胞内防御系统包括谷胱甘肽还原酶（GR）、硫氧还蛋白还原酶（TrxR）、超氧化物歧化酶（Sod）和过氧化氢酶（Cat）[2]。SOD和Cat构成了进化上保守的ROS防御系统，对抗超氧化物; SOD将超氧阴离子转化为H2 O2，Cat通过将H2 O2分解为氧气和水来防止自由羟基自由基的形成[2]。因此，它们是果蝇寿命决定中的重要效应子[3-7]。TrxR和GR的ROS防御更间接。它们分别将还原当量从NADPH转移至硫氧还蛋白（Trx）和谷胱甘肽二硫化物（GSSG），产生Trx（SH）2和谷胱甘肽（GSH），它们可作为有效的细胞内抗氧化剂[2，8]。发现TrxR和GR是分子保守的[9]。然而，果蝇[10，11]的单一GR同源物指定TrxR活性[12]，其补偿了用于再循环GSH的真正GR系统的缺乏[12]。我们发现，TrxR无效突变降低了充分保护细胞免受细胞毒性损伤的能力，导致幼虫死亡，而导致TrxR活性降低的突变会影响蛹羽化，并导致成虫寿命严重缩短。我们还提供了TrxR，Sod 1和Cat之间的功能相互作用的遗传证据，表明果蝇中ROS代谢的负担是由两个防御系统共享的。
Molecular oxygen is key to aerobic life but is also converted into cytotoxic byproducts referred to as reactive oxygen species (ROS) [1]. Intracellular defense systems that protect cells from ROS-induced damage include glutathione reductase (GR), thioredoxin reductase (TrxR), superoxide dismutase (Sod), and catalase (Cat) [2]. Sod and Cat constitute an evolutionary conserved ROS defense system against superoxide; Sod converts superoxide anions to H2O2, and Cat prevents free hydroxyl radical formation by breaking down H2O2 into oxygen and water [2]. As a consequence, they are important effectors in the life span determination of the fly Drosophila [3-7]. ROS defense by TrxR and GR is more indirect. They transfer reducing equivalents from NADPH to thioredoxin (Trx) and glutathione disulfide (GSSG), respectively, resulting in Trx(SH)2 and glutathione (GSH), which act as effective intracellular antioxidants [2, 8]. TrxR and GR were found to be molecularly conserved [9]. However, the single GR homolog of Drosophila [10, 11] specifies TrxR activity [12], which compensates for the absence of a true GR system for recycling GSH [12]. We show that TrxR null mutations reduce the capacity to adequately protect cells from cytotoxic damage, resulting in larval death, whereas mutations causing reduced TrxR activity affect pupal eclosion and cause a severe reduction of the adult life span. We also provide genetic evidence for a functional interaction between TrxR, Sod1, and Cat, indicating that the burden of ROS metabolism in Drosophila is shared by the two defense systems.