Human epidermal keratinocytes accumulate superoxide due to low activity of Mn-SOD, leading to mitochondrial functional impairment
Human epidermal keratinocytes accumulate superoxide due to low activity of Mn-SOD, leading to mitochondrial functional impairment
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DOI：
10.1038/sj.jid.5700666
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发表时间：
2007-05-01
影响因子：
6.5
通讯作者：
Schauen, Matthias
中科院分区：
文献类型：
--
作者：
Hornig-Do, Hue-Tran;von Kleist-Retzow, Juergen-Christoph;Schauen, Matthias
表皮的能量代谢一直是争议的话题。因此，我们在细胞培养物和人类皮肤切片中表征了人类原代角质形成细胞和成纤维细胞的线粒体表型。我们发现角质形成细胞的呼吸作用与成纤维细胞一样多，然而，呼吸链 (RC) 复合物的最大活性要低 2 至 5 倍，而 RC 蛋白的表达水平相似。乌头酸酶和异柠檬酸脱氢酶（两种特别容易受到超氧化物影响的线粒体酶）的最大活性低于成纤维细胞。事实上，角质形成细胞中的超氧阴离子水平要高得多，并且角质形成细胞表现出较高的脂质过氧化水平和较低的还原型谷胱甘肽/氧化型谷胱甘肽比率，表明氧化应激增强。尽管超氧化物歧化酶活性，尤其是线粒体超氧化物歧化酶 Mn-SOD 的表达在角质形成细胞中显着降低，这解释了高超氧化物水平，但谷胱甘肽过氧化物酶活性和蛋白质在成纤维细胞中几乎检测不到。过氧化氢酶活性和过氧化氢水平相似。总之，我们可以证明角质形成细胞不仅积极利用线粒体 RC 进行 50 三磷酸腺苷合成，而且还用于超氧阴离子的积累，甚至以牺牲线粒体功能为代价，这表明超氧化物驱动的线粒体损伤可能是角质形成细胞分化的先决条件。
The energy metabolism of the epidermis has been the subject of controversy; thus we characterized the mitochondrial phenotype of human primary keratinocytes and fibroblasts, in cell culture and in human skin sections. We found that keratinocytes respire as much as fibroblasts, however, maximal activities of the respiratory chain (RC) complexes were 2- to 5-fold lower, whereas expression levels of RC proteins were similar. Maximal activities of aconitase and isocitrate dehydrogenase, two mitochondrial enzymes especially vulnerable to superoxide, were lower than in fibroblasts. Indeed, superoxide anion levels were much higher in keratinocytes, and keratinocytes displayed higher lipid peroxidation levels and a lower reduced glutathione/oxidized glutathione ratio, indicating enhanced oxidative stress. Although superoxide dismutase activity and especially expression of the mitochondrial superoxide dismutase, Mn-SOD, were drastically lower in keratinocytes, explaining the high superoxide levels, glutathione peroxidase activity and protein were almost undetectable in fibroblasts. Catalase activity and hydrogen peroxide levels were similar. In summary, we could show that keratinocytes actively use the mitochondrial RC not only for adenosine 50 triphosphate synthesis but also for the accumulation of superoxide anions, even at the expense of mitochondrial functional capacity, indicating that superoxide-driven mitochondrial impairment might be a prerequisite for keratinocyte differentiation.