Reply to 'Role of glucose-6-phosphate dehydrogenase for oxidative stress and apoptosis'
Reply to 'Role of glucose-6-phosphate dehydrogenase for oxidative stress and apoptosis'
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DOI：
10.1038/sj.cdd.4401808
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发表时间：
2006-03-01
影响因子：
12.4
通讯作者：
Filosa, S
中科院分区：
文献类型：
--
作者：
Fico, A;Paglialunga, F;Filosa, S
在“葡萄糖-6-磷酸脱氢酶在氧化应激和凋亡中的作用”一文中，Efferth等人1总结了支持G6 PD在保护免受氧化还原应激诱导的凋亡中的作用的报告。其中，作者还提到了我们在《细胞死亡和分化》中描述的研究。2 Efferth等1将我们的研究与他们在1995年发表的研究进行了比较3，该研究描述了携带G6 PD突变（G6 PD亚琛）的外周血单核细胞（PMBC）的细胞凋亡诱导。在我们的论文中，我们研究了野生型和G6 pdD缺失（G6 pdD）小鼠胚胎干细胞（ES）中激活GSH氧化下游凋亡途径的信号事件。这些作者反对“G6 PD在保护免受氧化还原平衡诱导的细胞凋亡和坏死中的作用首次被明确指定”的说法，2声称这样的发现已在他们1995年的论文中报道过。3在我们看来，这两项研究没有可比性。Efferth等人3使用携带G6 PD突变亚琛的PMBC，但Kahn等人4已经描述了该变体的主要特征，特别是红细胞中的严重酶缺乏，与之形成对比的是在白色血细胞中观察到的几乎正常的活性。Efferth等人1还指出：“Pandolfi等人5报道G6 PD对于使用敲除小鼠防御氧化应激是必需的”，但Pandolfi等人5从未使用敲除小鼠，他们的研究在描述为G6 PD无效的小鼠ES细胞上进行。此外，在随后的论文中，相同的作者6发表了他们的ES细胞系保留了少量的G6 PD活性：因此，这些ES细胞系似乎是严重的G6 PD缺陷，而不是G6 PD无效。本论文首次对完全不能同时产生G6 PD和G6 pd转录本的ES G6 pdD进行了研究。7此外，Efferth等3，8分析了各种药物对细胞凋亡的诱导作用，包括细胞生长抑制药物（柔红霉素）、γ-辐射、糖皮质激素（地塞米松）和紫外线辐射。所有这些因素本身都不是氧化剂，但它们可以诱导细胞中不同类型的损伤（即酶，DNA和膜损伤的抑制），最终导致产生活性氧（ROS）。在这些条件下，很难确定细胞凋亡是由ROS诱导的，还是这些药物在G6 PD缺陷细胞中的协同作用所产生的损伤的结果。此外，在细胞凋亡损伤后，Efferth等人3，8没有检测GSH和NADPH及其氧化形式的水平，也没有测量ROS的产生，甚至没有分析
In the letter ‘Role of glucose-6–phosphate dehydrogenase for oxidative stress and apoptosis’, Efferth et al. 1 summarised reports favouring the role of G6PD in protection from redoxstress-induced apoptosis. Therein, the authors also referred to our studies described in Cell Death and Differentiation. 2 Efferth et al. 1 compared our study with the one they published in 19953 describing the induction of apoptosis in peripheral mononuclear cells (PMBC) carrying a G6PD mutation (G6PD Aachen). In our paper, 2 we investigated in wild-type and G6pd-deleted (G6pdD) mouse embryonic stem (ES) cells the signalling events activating an apoptotic pathway downstream GSH oxidation. These authors objected against the statement ‘for the first time a role for G6PD in the protection from redoximbalance-induced apoptosis and necrosis has been clearly assigned’, 2 claming that such a finding was reported in their 1995 paper. 3In our opinion, the two studies are not comparable. Efferth et al. 3 used PMBC carrying the G6PD mutation Aachen, but Kahn et al. 4 had already described the main characteristics of this variant and, in particular, the severe enzyme deficiency in erythrocytes, contrasting with an almost normal activity observed in white blood cells. Efferth et al. 1 also state:‘Pandolfi et al. 5 reported G6PD is essential for defence against oxidative stress using knockout mice’, but Pandolfi et al. 5 never used knockout mice, their study carried out on mouse ES cells described to be G6PD null. In addition, in a successive paper, the same authors6 published that their ES cell lines retain a small amount of G6PD activity: thus, these ES cell lines appear to be severely G6PD deficient rather than G6PD null. In our paper, 2 the study was carried out, for the first time, on ES G6pdD, which are completely unable to produce both G6pd transcript and G6PD. 7 Moreover, Efferth et al. 3, 8 analyse the induction of apoptosis by various agents including cytostatic drugs (daunorubicin), gamma-irradiation, glucocorticoids (dexamethasone) and UV irradiation. All these factors are not oxidative agents per se, but they can induce different kinds of damages in the cells (ie inhibition of enzymes, DNA and membrane damages), ultimately leading to generate reactive oxygen species (ROS). Under these conditions, it is difficult to ascertain whether apoptosis is induced by ROS, or is the result of damages produced by the synergistic effects of these agents in G6PD-deficient cells. In addition, after the apoptotic insult, Efferth et al. 3, 8 did not test the levels of GSH and NADPH and of their oxidised forms, nor measured the production of ROS and did not even analyse