Homocysteine induces melanocytes apoptosis via PERK-eIF2α-CHOP pathway in vitiligo
Homocysteine induces melanocytes apoptosis via PERK-eIF2α-CHOP pathway in vitiligo
复制标题
同型半胱氨酸通过 PERK-eIF2 α-CHOP 通路诱导白癜风黑素细胞凋亡
DOI：
10.1042/cs20200218
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发表时间：
2020-05-01
期刊：
影响因子：
6
通讯作者：
Li, Shuli
中科院分区：
文献类型：
--
作者：
Chen, Jiaxi;Zhuang, Tongtian;Li, Shuli
白癜风是一种色素脱失障碍，是由于表皮黑素细胞逐渐消失而发展起来的。氨基酸代谢产物同型半胱氨酸(Hcy)水平的升高被认为是氧化应激的循环标志，并被认为是白癜风的危险因素。然而，Hcy调节黑素细胞破坏的机制目前尚不清楚。本研究旨在阐明同型半胱氨酸对黑素细胞的破坏作用及其在白癜风发病机制中的作用。结果表明，进展性白癜风患者血清Hcy水平明显升高。值得注意的是，Hcy通过激活活性氧簇(ROS)和内质网(ER)应激蛋白激酶RNA样ER激酶(PERK)-真核细胞翻译起始因子2α(eIF2α)-C/EBP同源蛋白(CHOP)途径诱导黑素细胞凋亡。更重要的是，在Hcy转化过程中起作用的叶酸可以降低细胞内Hcy水平，进而逆转Hcy对黑素细胞的凋亡作用。此外，Hcy干扰黑素细胞的黑素合成，而补充叶酸可以逆转Hcy诱导的黑素细胞黑素合成缺陷。综上所述，进展期白癜风患者的Hcy水平显著升高，我们的体外研究表明，叶酸可以保护黑素细胞免受Hcy诱导的黑素细胞凋亡和黑素合成的抑制，表明叶酸是一种潜在的有益于进展期白癜风患者的药物。
Vitiligo is a depigmentation disorder that develops as a result of the progressive disappearance of epidermal melanocytes. The elevated level of amino acid metabolite homocysteine (Hcy) has been identified as circulating marker of oxidative stress and known as a risk factor for vitiligo. However, the mechanism underlying Hcy-regulated melanocytic destruction is currently unknown. The present study aims to elucidate the effect of Hcy on melanocytic destruction and its involvement in the pathogenesis of vitiligo. Our results showed that Hcy level was significantly elevated in the serum of progressive vitiligo patients. Notably, Hcy induced cell apoptosis in melanocytes via activating reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2 alpha (eIF2 alpha)-C/EBP homologous protein (CHOP) pathway. More importantly, folic acid, functioning in the transformation of Hcy, could lower the intracellular Hcy level and further reverse the apoptotic effect of Hcy on melanocytes. Additionally, Hcy disrupted melanogenesis whereas folic acid supplementation could reverse the melanogenesis defect induced by Hcy inmelanocytes. Taken together, Hcy is highly increased in vitiligo patients at progressive stage, and our in vitro studies revealed that folic acid could protect melanocytes from Hcy-induced apoptosis and melanin synthesis inhibition, indicating folic acid as a potential benefit agent for patients with progressive vitiligo.