1-phenyl 2-thiourea (PTU) activates autophagy in zebrafish embryos
1-phenyl 2-thiourea (PTU) activates autophagy in zebrafish embryos
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DOI：
10.1080/15548627.2020.1755119
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发表时间：
2020-04-23
期刊：
影响因子：
13.3
通讯作者：
Ma, Alvin Chun-Hang
中科院分区：
文献类型：
--
作者：
Chen, Xiang-Ke;Kwan, Joseph Shiu-Kwong;Ma, Alvin Chun-Hang
1-苯基2-硫脲（PTU）是一种酪氨酸酶抑制剂，广泛用于阻断斑马鱼（Danio rerio）胚胎的色素沉着和改善光学透明度。在这里，我们报告了一个以前未描述的影响PTU对斑马鱼胚胎的macroautophagy/自噬。在0.003%PTU处理后，在斑马鱼胚胎的各种组织和器官，如皮肤、脑和肌肉中观察到异常的自噬体和自溶酶体形成、溶酶体积累和自噬通量升高。与PTU处理相似，在体细胞tyr突变体斑马鱼胚胎中也观察到自噬激活和溶酶体积累，这表明Tyr抑制可能有助于PTU诱导的自噬激活。此外，我们证明了自噬有助于色素沉着抑制，但不是必不可少的PTU诱导的色素沉着抑制。随着自噬在生理和病理过程中的广泛参与以及PTU在斑马鱼自噬相关过程研究中的常规使用，这些观察结果在使用PTU处理的斑马鱼胚胎的自噬相关研究中引起了新的关注。
1-phenyl 2-thiourea (PTU) is a Tyr (tyrosinase) inhibitor that is extensively used to block pigmentation and improve optical transparency in zebrafish (Danio rerio) embryo. Here, we reported a previously undescribed effect of PTU on macroautophagy/autophagy in zebrafish embryos. Upon 0.003% PTU treatment, aberrant autophagosome and autolysosome formation, accumulation of lysosomes, and elevated autophagic flux were observed in various tissues and organs of zebrafish embryos, such as skin, brain, and muscle. Similar to PTU treatment, autophagic activation and lysosomal accumulation were also observed in the somatic tyr mutant zebrafish embryos, which suggest that Tyr inhibition may contribute to PTU-induced autophagic activation. Furthermore, we demonstrated that autophagy contributes to pigmentation inhibition, but is not essential to the PTU-induced pigmentation inhibition. With the involvement of autophagy in a wide range of physiological and pathological processes and the routine use of PTU in zebrafish research of autophagy-related processes, these observations raise a novel concern in autophagy-related studies using PTU-treated zebrafish embryos.