Mitochondrial impairment in peripheral blood mononuclear cells during the active phase of vitiligo
Mitochondrial impairment in peripheral blood mononuclear cells during the active phase of vitiligo
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DOI：
10.1046/j.0022-202x.2001.01459.x
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发表时间：
2001-10-01
影响因子：
6.5
通讯作者：
Picardo, M
中科院分区：
文献类型：
--
作者：
Dell'Anna, ML;Maresca, V;Picardo, M
关于白癜风的发病机制已经提出了几种假说，其中一些假说认为白癜风与疾病的病程有关。已有证据表明，氧化应激是黑素细胞退化的初始事件。根据这一观点，我们测定了活动期或稳定期白癜风患者和健康对照组红细胞和/或外周血单核细胞中超氧化物歧化酶、过氧化氢酶、还原型谷胱甘肽和维生素E的水平。在红细胞中，评估的参数没有显着差异。相反，在外周血单核细胞中，两组患者的超氧化物歧化酶活性均升高，而过氧化氢酶活性、还原型谷胱甘肽和维生素E水平仅在活动期疾病患者中降低。抗氧化剂的失衡与线粒体损伤导致的活性氧产生过多有关，因为通透性转换孔开放的抑制剂环孢菌素A显著减少了活性氧的产生。此外，在活动期白癜风患者中观察到线粒体跨膜电位的改变和更高比例的凋亡细胞。根据这些结果，我们认为，在白癜风中，线粒体可能是不同刺激的靶点，如活性氧的产生、细胞因子的产生、儿茶酚胺的释放、钙代谢的改变，所有这些都能诱导黑素细胞变性。
Several hypotheses have been made about the pathogenesis of vitiligo, and some of them have considered a systemic involvement in the course of the disease. Evidence has been presented on the role of oxidative stress as the initial event in melanocyte degeneration. In accordance with this view, we determined the levels of some antioxidants, i.e., superoxide dismutase, catalase, reduced glutathione, and vitamin E, in erythrocytes and/or peripheral blood mononuclear cells from patients with active or stable vitiligo and from a control group of healthy subjects. In erythrocytes the parameters evaluated were not significantly different. On the contrary, in peripheral blood mononuclear cells, superoxide dismutase activity was increased in both groups of patients, whereas catalase activity, reduced glutathione and vitamin E levels were decreased exclusively in subjects with active disease. The imbalance of antioxidants was associated with hyperproduction of reactive oxygen species due to a mitochondrial impairment as cyclosporin A, an inhibitor of the permeability transition pores opening, significantly reduced the reactive oxygen species production. Moreover an alteration of the mitochondrial transmembrane potential and a higher percentage of apoptotic cells were observed in active vitiligo patients. Based on these results, we suggest that, in vitiligo, mitochondria might be the target of different stimuli, such as reactive oxygen species generation, cytokines production, catecholamine release, alteration of Ca2+ metabolism, all of which capable of inducing melanocyte degeneration.