Detection of Misdistribution of Tyrosinase from Melanosomes to Lysosomes and Its Upregulation under Psoralen/Ultraviolet A with a Melanosome-Targeting Tyrosinase Fluorescent Probe

	Detection of Misdistribution of Tyrosinase from Melanosomes to Lysosomes and Its Upregulation under Psoralen/Ultraviolet A with a Melanosome-Targeting Tyrosinase Fluorescent Probe
	Zhou, Jin; Shi, Wen; Li, Lihong; Gong, Qiu-Yu; Wu, Xiaofeng; Li, Xiaohua; Ma, Huimin
刊名	ANALYTICAL CHEMISTRY
	2016-04-19
卷号	88 期号:8 页码:4557-4564
英文摘要	Tyrosinase is regarded as an important biomarker of melanoma cancer, and its metabolism is closely related to some severe skin diseases such as vitiligo. Since tyrosinase is mainly located in the melanosomes of melanocytes, a probe that can specifically detect and image tyrosinase in melanosomes would be in urgent demand to study the behavior of the enzyme in cells, but unfortunately, no melanosome-targeting tyrosinase fluorescent probe has been reported so far to the bet of our knowledge. In this work, we have developed such a new probe, Mela-TYR, which bears morpholine as a melanosome-targeting group and 4aminophenol as a tyrosinase reaction group. The probe exhibits not only a highly sensitive and selective off-on response to tyrosinase via oxidization cleavage, but also an accurate targeting ability toward the acidic organelles of melanosomes and lyososomes, which is validated by colocalization experiments with mCherry-tagged melanosomes as well as DND-99 (a commercial dye). The probe has been used to image the relative contents of tyrosinase in different cells. Notably, because of the tyrosinase deficiency in normal lysosomes, the probe only fluoresces in melanosomes in principle although it can accumulate in other acidic organelles like lysosomes. By virtue of this property, the misdistribution of tyrosinase from melanosomes to lysosomes in murine melanoma B16 cells under the stimulation of inulavosin is imaged in real time for the first time. Moreover, the upregulation of melanosomal tyrosinase in live B16 cells under the stimulation of psoralen/ultraviolet A is detected with our probe, and this upregulation is further verified by standard colorimetric assay. The probe provides a simple, visual method to study the metabolism of tyrosinase in cells and shows great potential in clinical diagnosis and treatments of tyrosinase-associated diseases.
收录类别	SCI
语种	英语
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/36084]
专题	化学研究所_活体分析化学实验室
作者单位	Chinese Acad Sci, Inst Chem, Key Lab Analyt Chem Living Biosyst, Beijing Natl Lab Mol Sci, Beijing 100190, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Jin,Shi, Wen,Li, Lihong,et al. Detection of Misdistribution of Tyrosinase from Melanosomes to Lysosomes and Its Upregulation under Psoralen/Ultraviolet A with a Melanosome-Targeting Tyrosinase Fluorescent Probe[J]. ANALYTICAL CHEMISTRY,2016,88(8):4557-4564.
APA	Zhou, Jin.,Shi, Wen.,Li, Lihong.,Gong, Qiu-Yu.,Wu, Xiaofeng.,...&Ma, Huimin.(2016).Detection of Misdistribution of Tyrosinase from Melanosomes to Lysosomes and Its Upregulation under Psoralen/Ultraviolet A with a Melanosome-Targeting Tyrosinase Fluorescent Probe.ANALYTICAL CHEMISTRY,88(8),4557-4564.
MLA	Zhou, Jin,et al."Detection of Misdistribution of Tyrosinase from Melanosomes to Lysosomes and Its Upregulation under Psoralen/Ultraviolet A with a Melanosome-Targeting Tyrosinase Fluorescent Probe".ANALYTICAL CHEMISTRY 88.8(2016):4557-4564.