Botulinum neurotoxin type DC (BoNT/DC) cleavage of VAMP3 reduces melanin production in melanocytes

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon Pub Date : 2025-04-24 DOI:10.1016/j.toxicon.2025.108372

Shiazah Malik , Linh Le , Raymond E. Boissy , Amy Brideau-Andersen , Birgitte Sondergaard

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Abstract

Melanin in skin and hair protects cells from UV damage; however, uneven skin color or hyperpigmentation is a common aesthetic concern. Melanin is synthesized in melanosomes, organelles within melanocytes, where tyrosinase converts tyrosine to melanin. Trafficking of tyrosinase or other cargo (eg, premelanosome protein [PMEL]) may depend on vesicle-associated membrane proteins (VAMPs); interfering with VAMPs has been reported to impact melanogenesis. Botulinum neurotoxin type DC (BoNT/DC) is a naturally occurring mosaic serotype that cleaves the SNARE proteins VAMP1-3. This study evaluated BoNT/DC as a potential treatment for hyperpigmentation by testing if it affects melanogenesis. In melanocytes, BoNT/DC cleaved VAMP2 and VAMP3, and knockdown of VAMP3, but not VAMP2, reduced melanin content, which suggests that BoNT/DC may affect melanogenesis via VAMP3 cleavage. Indeed, BoNT/DC (5 nM) produced a ∼50 % reduction in melanin content in melanocytes, and in 2 human melanocyte models, BoNT/DC, but not BoNT/A, significantly reduced melanin content (∼40–50 %) without cytotoxicity. Electron microscopy showed that BoNT/DC-treated melanocytes contained more early-stage (II) and fewer late-stage (IV) melanosomes than vehicle- or BoNT/A-treated melanocytes. Overall, BoNT/DC reduced melanin content in multiple melanocyte models, and its lightening effects are likely due to VAMP3 cleavage interfering with trafficking of cargo (eg, tyrosinase, PMEL) required for melanogenesis.

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肉毒杆菌神经毒素型DC （BoNT/DC）切割VAMP3可减少黑色素细胞中黑色素的产生

皮肤和头发中的黑色素可以保护细胞免受紫外线的伤害；然而，不均匀的肤色或色素沉着是一个常见的审美问题。黑色素是在黑素小体中合成的，黑素小体是黑素细胞内的细胞器，酪氨酸酶将酪氨酸转化为黑色素。酪氨酸酶或其他货物（如黑素体前蛋白[PMEL]）的运输可能依赖于囊泡相关膜蛋白（VAMPs）；据报道，干扰VAMPs会影响黑色素生成。肉毒杆菌神经毒素型DC （BoNT/DC）是一种自然发生的马赛克血清型，可切割SNARE蛋白VAMP1-3。本研究通过测试BoNT/DC是否影响黑色素生成来评估BoNT/DC作为色素沉着症的潜在治疗方法。在黑色素细胞中，BoNT/DC可切割VAMP2和VAMP3，而VAMP3的敲低可降低黑色素含量，这表明BoNT/DC可能通过切割VAMP3影响黑色素的形成。事实上，BoNT/DC （5 nM）使黑素细胞中的黑色素含量降低了~ 50%，并且在2个人类黑素细胞模型中，BoNT/DC（而不是BoNT/ a）显著降低了黑色素含量（~ 40 - 50%），而没有细胞毒性。电镜显示，BoNT/ dc处理的黑素细胞比对照或BoNT/ a处理的黑素细胞含有更多的早期（II）和更少的晚期（IV）黑素体。总体而言，BoNT/DC降低了多种黑素细胞模型中的黑色素含量，其美白效果可能是由于VAMP3的切割干扰了黑色素生成所需的货物运输（例如酪氨酸酶，PMEL）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicon 医学-毒理学

CiteScore

4.80

自引率

10.70%

发文量

358

审稿时长

68 days

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