Friedmann P S, Gilchrest B A
USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts 02111.
J Cell Physiol. 1987 Oct;133(1):88-94. doi: 10.1002/jcp.1041330111.
In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of 14C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfold differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms.
在人类中，皮肤色素沉着的主要刺激因素是紫外线辐射（UVR）。对于这种反应背后的机制知之甚少，部分原因是整个表皮中相互作用的复杂性。使用最近开发的培养系统，将人类黑素细胞每天暴露于来自太阳模拟器的生理范围内的UVR剂量。在最后一次暴露后24小时测定反应。每个细胞的黑色素含量和14C-DOPA摄取量呈剂量相关增加，同时伴有生长抑制。来自不同种族起源供体的细胞黑色素增加比例相似，尽管基础值存在约十倍的差异。光镜和电镜显示UVR刺激后树突化增加，以及黑素体数量和黑素化程度增加，类似于完整皮肤暴露于阳光下后黑素细胞的公认变化。Cloudman S91黑色素瘤细胞也观察到类似反应，尽管这种鼠细胞系需要较低的UVR剂量和较少的暴露次数以实现最大刺激。这些数据表明UVR能够直接刺激黑色素生成。由于在某些情况下环磷酸腺苷（cAMP）升高与培养的黑素细胞色素生成增加有关，因此进行了初步实验以观察UVR的作用是否由cAMP介导。作为阳性对照，α-促黑素（alpha-MSH）和异丁基甲基黄嘌呤（IBMX）均使人类黑素细胞和/或S91细胞中的cAMP水平增加四倍，但在给予足以刺激色素生成的UVR剂量后，暴露后长达4小时cAMP水平没有变化。因此，似乎UVR诱导的黑色素生成是由cAMP非依赖性机制介导的。
