Pankovich J M, Jimbow K, Ito S
Division of Dermatology and Cutaneous Sciences, University of Alberta, Edmonton, Canada.
Pigment Cell Res. 1990 Sep;3(3):146-9. doi: 10.1111/j.1600-0749.1990.tb00279.x.
A phenolic amine compound, 4-S-cysteaminylphenol (4-S-CAP), was found to cause a selective destruction of follicular melanocytes. It was also recently found that 4-S-CAP can be a substrate for both tyrosinase and plasma monoamine oxidase (MAO). Both of these enzymes are capable of producing cytotoxic intermediates through their interaction with 4-S-CAP. To study the mechanism of selective melanocytotoxicity of phenolic amine compounds, we compared the in vivo depigmenting potency of 4-S-CAP and its three analogues; i.e., 4-S-HomoCAP, alpha-methyl(Me)-4-S-CAP and N,N-dimethyl(DiMe)-4-S-CAP, using black hair follicles. All four of these phenolic amine compounds possessed depigmenting potency. In this study we examined the kinetics of tyrosinase and MAO by these four compounds. 4-S-CAP and 4-S-HomoCAP were the substrates of both tyrosinase and MAO, whereas alpha-Me-4-S-CAP and N,N-DiMe-4-S-CAP were the substrates of tyrosinase alone. The rate of o-quinone formation by tyrosinase was not in parallel to the in vivo depigmenting potency of the tested compounds. It is therefore indicated that plasma MAO is not the enzyme directly responsible for the production of the melanocytotoxic intermediates from the phenolic amine compounds. We also found that the observed in vivo depigmentation results from complex processes involving the amount of o-quinone formed and the intracellular interaction of o-quinone with protein species.
一种酚胺化合物，4-S-半胱氨酰苯酚（4-S-CAP），被发现会导致毛囊黑素细胞的选择性破坏。最近还发现4-S-CAP可以作为酪氨酸酶和血浆单胺氧化酶（MAO）的底物。这两种酶都能够通过与4-S-CAP相互作用产生细胞毒性中间体。为了研究酚胺化合物选择性黑素细胞毒性的机制，我们使用黑色毛囊比较了4-S-CAP及其三种类似物，即4-S-高半胱氨酰苯酚、α-甲基（Me）-4-S-CAP和N，N-二甲基（DiMe）-4-S-CAP的体内脱色能力。所有这四种酚胺化合物都具有脱色能力。在本研究中，我们研究了这四种化合物对酪氨酸酶和MAO的动力学影响。4-S-CAP和4-S-高半胱氨酰苯酚是酪氨酸酶和MAO的底物，而α-Me-4-S-CAP和N，N-二甲基-4-S-CAP仅是酪氨酸酶的底物。酪氨酸酶形成邻醌的速率与受试化合物的体内脱色能力不平行。因此表明血浆MAO不是直接负责从酚胺化合物产生黑素细胞毒性中间体的酶。我们还发现，观察到的体内色素脱失是由涉及邻醌形成量以及邻醌与蛋白质种类的细胞内相互作用的复杂过程导致的。
