Slominski A, Moellmann G, Kuklinska E
Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut 06510.
Pigment Cell Res. 1989 Mar-Apr;2(2):109-16. doi: 10.1111/j.1600-0749.1989.tb00170.x.
In cultured cells of the Bomirski Ab amelanotic hamster melanoma line, the substrates of tyrosinase, L-tyrosine, and L-DOPA induce the melanogenic pathway. In this report, we demonstrate that these substrates regulate the subcellular apparatus involved in their own metabolism and that this regulation is under the dynamic control of one of the components of this apparatus, tyrosinase, via tyrosine hydroxylase activity. Culturing cells with nontoxic but melanogenically inhibitory levels of phenylthiourea (PTU; 100 microM) strongly inhibits induction of both the tyrosine hydroxylase and DOPA oxidase activities of tyrosinase by L-tyrosine (200 microM) but has no effect on the induction of either activity by L-DOPA (50 microM). De novo synthesis of premelanosomes precedes the onset of tyrosine-induced melanogenesis. Thereafter, increases in the population of melanosomes (likewise inhibited by PTU) correlate positively with increases in tyrosinase activity induced by L-tyrosine. Melanogenesis induced by L-DOPA in the absence of L-tyrosine is rate-limited not by tyrosinase but by inadequate melanosome synthesis. Our findings indicate that in Bomirski Ab amelanotic hamster melanoma cells the synthesis of the subcellular apparatus of melanogenesis is initiated by L-tyrosine and is regulated further by tyrosinase and L-DOPA, which serves as a second messenger subsequent to tyrosine hydroxylase activity.
在博米尔斯基（Bomirski）无黑色素仓鼠黑色素瘤细胞系的培养细胞中，酪氨酸酶的底物L-酪氨酸和L-多巴可诱导黑色素生成途径。在本报告中，我们证明这些底物调节参与其自身代谢的亚细胞机制，并且这种调节受该机制的一个组成部分酪氨酸酶通过酪氨酸羟化酶活性的动态控制。用无毒但具有黑色素生成抑制水平的苯硫脲（PTU；100微摩尔）培养细胞，可强烈抑制L-酪氨酸（200微摩尔）对酪氨酸酶的酪氨酸羟化酶和多巴氧化酶活性的诱导，但对L-多巴（50微摩尔）诱导的任何一种活性均无影响。前黑素小体的从头合成先于酪氨酸诱导的黑色素生成开始。此后，黑素小体数量的增加（同样受PTU抑制）与L-酪氨酸诱导的酪氨酸酶活性的增加呈正相关。在没有L-酪氨酸的情况下，L-多巴诱导的黑色素生成的限速因素不是酪氨酸酶，而是黑素小体合成不足。我们的研究结果表明，在博米尔斯基无黑色素仓鼠黑色素瘤细胞中，黑色素生成的亚细胞机制的合成由L-酪氨酸启动，并进一步受酪氨酸酶和L-多巴的调节，L-多巴在酪氨酸羟化酶活性之后作为第二信使。
