Carboxyfullerenes protect human keratinocytes from ultraviolet-B-induced apoptosis

Carboxyfullerenes protect human keratinocytes from ultraviolet-B-induced apoptosis
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DOI:
10.1046/j.1523-1747.2000.00140.x
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发表时间:
2000-11-01
影响因子:
6.5
通讯作者:
Pincelli, C
Pincelli, C
中科院分区:
医学1区
文献类型:
--
作者:
Fumelli, C;Marconi, A;Pincelli, C

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羧基富勒烯是富勒烯的一种水溶性羧酸衍生物,具有自由基清除剂的作用,研究了其作为抗紫外线诱导的人角质形成细胞损伤的保护剂的作用。首先,我们证明了羧基富勒烯对这些细胞没有细胞毒性。此外,该化合物显著降低紫外线-B-诱导的角质形成细胞增殖的抑制,并以时间和剂量依赖性方式保护角质形成细胞免于由紫外线B照射引起的凋亡。此外,细胞与去极化的线粒体的百分比是显着较低的紫外线-B-照射的角质形成细胞预处理的羧基富勒烯比单独提供的稀释剂的细胞。羧基富勒烯还保护人类角质形成细胞免于暴露于脱氧-D-核糖诱导的凋亡,脱氧-D-核糖是一种通过涉及氧化应激的途径导致细胞死亡的糖。另一方面,紫外线B下调人类角质形成细胞中的bcl-2水平,而羧基富勒烯未能阻止这种作用。这些结果表明,羧基富勒烯保护人角质形成细胞免受紫外线B损伤,可能是通过一种机制,干扰活性氧的产生从去极化线粒体没有bcl-2的参与。
Carboxyfullerene, a water-soluble carboxylic acid derivative of a fullerene, which acts as a free-radical scavenger, was investigated as a protective agent against ultraviolet-light-induced damage in human keratinocytes. First, we demonstrate that carboxyfullerene is not cytotoxic for these cells. In addition, this compound significantly reduces the ultraviolet-B-induced inhibition of keratinocyte proliferation and protects keratinocytes from apoptosis caused by ultraviolet B irradiation in a time- and dose-dependent fashion. Furthermore, the percentage of cells with depolarized mitochondria is significantly lower in ultraviolet-B-irradiated keratinocytes pretreated with carboxyfullerene than in cells provided with diluent alone. Carboxyfullerene also protects human keratinocytes from apoptosis induced by exposure to deoxy-D-ribose, a sugar that causes cell death through a pathway involving oxidative stress. On the other hand, ultraviolet B downregulates bcl-2 levels in human keratinocytes, and carboxyfullerene fails to prevent this effect. These results suggest that carboxy- fullerene protects human keratinocytes from ultraviolet B damage possibly via a mechanism interfering with the generation of reactive oxygen species from depolarized mitochondria without the involvement of bcl-2.