sAPPalpha, the soluble form of the beta-amyloid precursor protein, has been shown to act as a potent epidermal growth factor by stimulating keratinocyte proliferation and migration. In this report we provide evidence for a cytoprotective role of sAPPalpha. As a model we used HaCaT cells and normal human keratinocytes (NHK) cultured in the absence of fetal calf serum and bovine pituitary extract. Under these conditions keratinocytes began to undergo apoptosis at increasing rates after 96 h of culture. Surprisingly, keratinocytes were protected from apoptosis by the addition of 50 nM recombinant sAPPalpha. Subsequent experiments were performed to elucidate the regulatory basis of the cytoprotective role of sAPPalpha. We found that recombinant sAPPalpha facilitated the substrate adhesion of keratinocytes in the first 30 minutes after seeding. The basis for this adhesion-promoting function was shown by the ability of recombinant sAPPalpha to continuously coat the culture dish thereby promoting the ability to bind keratinocytes. A second mechanism explaining the cytoprotective role was found in the significant inhibition of apoptosis by recombinant sAPPalpha. In HaCaT cells moderate UV-B irradiation was sufficient to induce apoptosis. In contrast, induction of apoptosis in NHK required additionally the depletion of endogenous sAPPalpha suggesting that sAPPalpha mediates protection against UV-B irradiation. Staurosporine-induced apoptosis rates were significantly reduced by about 59% after addition of recombinant sAPPalpha. These results show that sAPPalpha exerts a pronounced cytoprotective effect and that this effect is mediated by facilitated cell adhesion and by the antiapoptotic function of sAPPalpha.

中文翻译：

---

sAppalpha在人角质形成细胞中的细胞保护功能。

sAPPalpha（β-淀粉样蛋白前体蛋白的可溶形式）已显示出通过刺激角质形成细胞增殖和迁移而充当有效的表皮生长因子。在本报告中，我们提供了sAPPalpha的细胞保护作用的证据。作为模型，我们使用了在没有胎牛血清和牛垂体提取物的情况下培养的HaCaT细胞和正常人角质形成细胞（NHK）。在这些条件下，培养96小时后，角质形成细胞开始以增加的速率发生凋亡。令人惊讶地，通过添加50 nM重组sAPPalpha保护角质形成细胞免于凋亡。进行了后续实验，以阐明sAPPalpha的细胞保护作用的调控基础。我们发现重组sAPPalpha在播种后的前30分钟内促进了角质形成细胞的基质粘附。重组sAPPalpha连续包被培养皿从而增强结合角质形成细胞的能力表明了这种促进粘附功能的基础。在重组sAPPalpha显着抑制细胞凋亡中发现了第二个解释细胞保护作用的机制。在HaCaT细胞中，适度的UV-B照射足以诱导细胞凋亡。相比之下，在NHK中诱导细胞凋亡还需要消耗内源性sAPPalpha，这表明sAPPalpha介导了针对UV-B辐射的保护作用。加入重组sAPPalpha后，星形孢菌素诱导的凋亡率显着降低了约59％。