The organotelluride catalyst (PHTE)₂NQ prevents HOCl-induced systemic sclerosis in mouse.
The organotelluride catalyst (PHTE)₂NQ prevents HOCl-induced systemic sclerosis in mouse.
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有机碲化物催化剂 (PHTE)âNQ 可预防 HOCl 诱导的小鼠系统性硬化症
DOI：
10.1038/jid.2011.455
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
P. Batteux
中科院分区：
文献类型：
--
作者：
W. Marut;N. Kavian;A. Servenaz;C. Nicco;L.A. Ba;M. Doering;C. Chereau;C. Jacob;B. Weill;P. Batteux
系统性硬化症（SSc）是一种结缔组织疾病，其特征是皮肤和内脏纤维化、微血管损伤和自身免疫。HOCl诱导的小鼠SSc是模拟人类疾病的主要特征，特别是皮肤成纤维细胞的活化和过度增殖率的鼠模型。我们在这里证明了基于碲的催化剂2，3-双（苯基碲基）萘醌（（PHTE）2NQ）在小鼠SSc治疗中的效率，通过其对活化的SSc皮肤成纤维细胞的选择性细胞毒性作用。与未处理的小鼠SSc动物相比，用（PHTE）2NQ处理的SSc小鼠显示肺和皮肤纤维化以及皮肤中的α-平滑肌肌动蛋白（α-SMA）表达显著降低。晚期氧化蛋白产物、硝酸盐和抗DNA拓扑异构酶I自身抗体的血清浓度在SSc小鼠中增加，但在用（PHTE）2NQ治疗的SSc小鼠中显著降低。为了评估（PHTE）2NQ的作用机制，在正常成纤维细胞和小鼠SSc皮肤成纤维细胞中比较（PHTE）2NQ的细胞毒性作用。小鼠SSc成纤维细胞中的ROS产生高于正常成纤维细胞，并且仍被（PHTE）2NQ增加以达到致死阈值并杀死小鼠SSc成纤维细胞。因此，（PHTE）2NQ治疗小鼠SSc的有效性似乎与（PHTE）2NQ对过度增殖成纤维细胞的选择性促氧化和细胞毒性作用有关。
Systemic sclerosis (SSc) is a connective tissue disorder characterized by skin and visceral fibrosis, microvascular damage, and autoimmunity. HOCl-induced mouse SSc is a murine model that mimics the main features of the human disease, especially the activation and hyperproliferation rate of skin fibroblasts. We demonstrate here the efficiency of a tellurium-based catalyst 2,3-bis(phenyltellanyl)naphthoquinone ((PHTE)2NQ) in the treatment of murine SSc, through its selective cytotoxic effects on activated SSc skin fibroblasts. SSc mice treated with (PHTE)2NQ displayed a significant decrease in lung and skin fibrosis and in alpha-smooth muscle actin (α-SMA) expression in the skin compared with untreated mouse SSc animals. Serum concentrations of advanced oxidation protein products, nitrate, and anti-DNA topoisomerase I autoantibodies were increased in SSc mice, but were significantly reduced in SSc mice treated with (PHTE)2NQ. To assess the mechanism of action of (PHTE)2NQ, the cytotoxic effect of (PHTE)2NQ was compared in normal fibroblasts and in mouse SSc skin fibroblasts. ROS production is higher in mouse SSc fibroblasts than in normal fibroblasts, and was still increased by (PHTE)2NQ to reach a lethal threshold and kill mouse SSc fibroblasts. Therefore, the effectiveness of (PHTE)2NQ in the treatment of mouse SSc seems to be linked to the selective pro-oxidative and cytotoxic effects of (PHTE)2NQ on hyperproliferative fibroblasts.
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影响因子：
4.9
作者：
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DOI：
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发表时间：
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影响因子：
24.7
作者：
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DOI：
10.1056/nejmoa052955
发表时间：
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期刊：
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影响因子：
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作者：
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影响因子：
6.5
作者：
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