Martínez-Esparza M, Jiménez-Cervantes C, Beermann F, Aparicio P, Lozano J A, García-Borrón J C
Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, 30100 Espinardo, Murcia, Spain.
J Biol Chem. 1997 Feb 14;272(7):3967-72. doi: 10.1074/jbc.272.7.3967.
Current evidence suggests that melanogenesis is controlled by epidermal paracrine modulators. We have analyzed the effects of transforming growth factor-beta1 (TGF-beta1) on the basal melanogenic activities of B16/F10 mouse melanoma cells. TGF-beta1 treatment (48 h) elicited a concentration-dependent decrease in basal tyrosine hydroxylase and 3,4-dihydroxyphenylalanine (Dopa) oxidase activities, to less than 30% of the control values but had no effect on dopachrome tautomerase activity (TRP-2). The inhibition affected to similar extents the Dopa oxidase activity associated to tyrosinase-related protein-1 (TRP-1) and tyrosinase. This inhibition was noticeable between 1 and 3 h after the addition of the cytokine, and maximal after 6 h of treatment. The decrease in the enzymatic activity was paralleled by a decrease in the abundance of the TRP-1 and tyrosinase proteins. TGF-beta1 mediated this effect by increasing the rate of degradation of tyrosinase and TRP-1. Conversely, after 48 h of treatment, the expression of the tyrosinase gene decreased only slightly, while TRP-1 and TRP-2 gene expression was not affected. An increased rate of proteolytic degradation of TRP-1 and tyrosinase seems the main mechanism accounting for the inhibitory effect of TGF-beta1 on the melanogenic activity of B16/F10 cells.
目前的证据表明，黑色素生成受表皮旁分泌调节剂的控制。我们分析了转化生长因子-β1（TGF-β1）对B16/F10小鼠黑色素瘤细胞基础黑色素生成活性的影响。TGF-β1处理（48小时）导致基础酪氨酸羟化酶和3,4-二羟基苯丙氨酸（多巴）氧化酶活性呈浓度依赖性降低，降至对照值的30%以下，但对多巴色素互变异构酶活性（TRP-2）没有影响。这种抑制对与酪氨酸酶相关蛋白-1（TRP-1）和酪氨酸酶相关的多巴氧化酶活性影响程度相似。在加入细胞因子后1至3小时之间这种抑制作用明显，处理6小时后达到最大抑制。酶活性的降低与TRP-1和酪氨酸酶蛋白丰度的降低平行。TGF-β1通过增加酪氨酸酶和TRP-1的降解速率介导这种效应。相反，处理48小时后，酪氨酸酶基因的表达仅略有下降，而TRP-1和TRP-2基因的表达未受影响。TRP-1和酪氨酸酶蛋白水解降解速率的增加似乎是TGF-β1对B16/F10细胞黑色素生成活性产生抑制作用的主要机制。
