Yang F, Sarangarajan R, Le Poole I C, Medrano E E, Boissy R E
Department of Dermatology, University of Cincinnati, OH 45267-0592, USA.
J Invest Dermatol. 2000 Jan;114(1):157-64. doi: 10.1046/j.1523-1747.2000.00836.x.
It has been known for several decades that cutaneous depigmentation, i.e., contact/occupational vitiligo, can be caused by some phenolic derivatives that have a similar structure to tyrosine. Among these phenolic depigmenting agents, 4-tertiary butylphenol is the most potent. The cutaneous depigmentation induced by phenolic derivatives results from the loss of functional melanocytes. Tyrosinase is a melanocyte specific copper-containing enzyme that catalyzes the conversion of the amino acid tyrosine, through a complex series of intermediates, to melanin. In this study we tested the hypothesis that the cytotoxicity induced by 4-tertiary butylphenol is mediated by tyrosinase and occurs via an apoptotic process. Melanocyte cultures derived from African-American and Caucasian donors exhibiting a 3-fold difference in tyrosinase activity and 14-fold difference in melanin content demonstrate comparable concentration-dependent sensitivity to 4-tertiary butylphenol. In addition, cultures of dermal fibroblasts and epidermal keratinocytes exhibited similar and reduced sensitivity, respectively, to 4-tertiary butylphenol compared with autologous melanocytes. Two melanoma cell lines, one melanotic and one amelanotic lacking the expression of both tyrosinase protein and activity, when transfected with the tyrosinase cDNA, exhibited no alteration in its sensitivity to 4-tertiary butylphenol. These data suggest that 4-tertiary butylphenol cytotoxicity is not mediated via tyrosinase. Melanocytes treated with 4-tertiary butylphenol, however, did exhibit plasma membrane blebbing, DNA fragmentation, and phosphatidylserine relocalization indicating that 4-tertiary butylphenol induced melanocyte destruction occurs by an apoptotic process.
几十年来，人们已经知道皮肤色素脱失，即接触性/职业性白癜风，可由一些结构与酪氨酸相似的酚类衍生物引起。在这些酚类色素脱失剂中，4-叔丁基苯酚的作用最强。酚类衍生物引起的皮肤色素脱失是功能性黑素细胞丧失的结果。酪氨酸酶是一种黑素细胞特异性含铜酶，它通过一系列复杂的中间产物催化氨基酸酪氨酸转化为黑色素。在本研究中，我们测试了以下假设：4-叔丁基苯酚诱导的细胞毒性由酪氨酸酶介导，并通过凋亡过程发生。来自非裔美国人和白种人供体的黑素细胞培养物，其酪氨酸酶活性相差3倍，黑色素含量相差14倍，但对4-叔丁基苯酚表现出相当的浓度依赖性敏感性。此外，与自体黑素细胞相比，真皮成纤维细胞和表皮角质形成细胞培养物对4-叔丁基苯酚的敏感性分别相似且降低。两种黑色素瘤细胞系，一种有黑色素，一种无黑色素，均缺乏酪氨酸酶蛋白表达和活性，当转染酪氨酸酶cDNA时，其对4-叔丁基苯酚的敏感性未发生改变。这些数据表明，4-叔丁基苯酚的细胞毒性不是由酪氨酸酶介导的。然而，用4-叔丁基苯酚处理的黑素细胞确实表现出质膜起泡、DNA片段化和磷脂酰丝氨酸重新定位，表明4-叔丁基苯酚诱导的黑素细胞破坏是通过凋亡过程发生的。
