Catalytic function of Drosophila melanogaster glutathione S-transferase DmGSTS1-1 (GST-2) in conjugation of lipid peroxidation end products
Catalytic function of Drosophila melanogaster glutathione S-transferase DmGSTS1-1 (GST-2) in conjugation of lipid peroxidation end products
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DOI：
10.1046/j.1432-1327.2001.02179.x
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发表时间：
2001-05-01
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影响因子：
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通讯作者：
Zimniak, P
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作者：
Singh, SP;Coronella, JA;Zimniak, P
果蝇谷胱甘肽S转移酶DmGSTS1-1(早期命名为GST-2)与Sigma类GST相关，以前被描述为间接飞行肌肉相关蛋白，但尚不具有已知的催化特性。我们现在报道，从果蝇中分离或在大肠杆菌中表达的DmGSTS1-1对常用的合成底物1-氯-2，4-二硝基苯(CDNB)基本上没有活性，但对脂质过氧化产生的亲电醛4-羟基壬烯醛(4-HNE)具有较高的谷胱甘肽结合活性。4-HNE被认为具有信号功能，在较高浓度下，已被证明具有细胞毒性，并参与各种退行性疾病的病因学。携带GstS1基因P元件插入的果蝇菌株对4-HNE的谷胱甘肽结合能力降低。在两个、一个或没有GstS1等位基因被P元件插入干扰的果蝇中，DmGSTS1-1蛋白含量与4-HNE结合活性之间存在线性关系。这种相关性表明，在成年果蝇中，70+/-6%的4-HNE结合能力可归因于DmGSTS1-1。DmGSTS1-1的高丰度(约占成年果蝇可溶性蛋白的2%)，以及以前报道的在高度有氧组织(间接飞行肌肉)或对氧化损伤特别敏感的组织(神经元组织)中的定位，表明该酶可能对氧化应激的有害影响具有保护作用。昆虫的这种功能类似于哺乳动物中由专门的α类谷胱甘肽S转移酶(例如GSTA4-4)执行的功能。在谷胱甘肽S转移酶超家族的多个分支中独立出现了4-HNE结合活性，这表明4-HNE的分解代谢可能是有氧生命所必需的。
Drosophila melanogaster glutathione S-transferase DmGSTS1-1 (earlier designated as GST-2) is related to sigma class GSTs and was previously described as an indirect flight muscle-associated protein with no known catalytic properties. We now report that DmGSTS1-1 isolated from Drosophila or expressed in Escherichia coli is essentially inactive toward the commonly used synthetic substrate 1-chloro-2,4-dinitrobenzene (CDNB), but has relatively high glutathione-conjugating activity for 4-hydroxynonenal (4-HNE), an electrophilic aldehyde derived from lipid peroxidation. 4-HNE is thought to have signaling functions and, at higher concentrations, has been shown to be cytotoxic and involved in the etiology of various degenerative diseases. Drosophila strains carrying P-element insertions in the GstS1 gene have a reduced capacity for glutathione conjugation of 4-HNE. In flies with both, one, or none of the GstS1 alleles disrupted by P-element insertion, there is a linear correlation between DmGSTS1-1 protein content and 4-HNE-conjugating activity. This correlation indicates that in adult Drosophila 70 +/- 6% of the capacity to conjugate 4-HNE is attributable to DmGSTS1-1. The high abundance of DmGSTS1-1 (approximately 2% of the soluble protein in adult flies) and its previously reported localization in tissues that are either highly aerobic (indirect flight muscle) or especially sensitive to oxidative damage (neuronal tissue) suggest that the enzyme may have a protective role against deleterious effects of oxidative stress. Such function in insects would be analogous to that carried out in mammals by specialized alpha class glutathione S-transferases (e.g. GSTA4-4). The independent emergence of 4-HNE-conjugating activity in more than one branch of the glutathione S-transferase superfamily suggests that 4-HNE catabolism may be essential for aerobic life.