In vivo imaging of leucine aminopeptidase activity in drug-induced liver injury and liver cancer via a near-infrared fluorescent probe.
In vivo imaging of leucine aminopeptidase activity in drug-induced liver injury and liver cancer via a near-infrared fluorescent probe.
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通过近红外荧光探针对药物性肝损伤和肝癌中亮氨酸氨肽酶活性进行体内成像
DOI：
10.1039/c6sc05712h
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发表时间：
2017-05-01
期刊：
影响因子：
8.4
通讯作者：
Ma H
中科院分区：
文献类型：
--
作者：
He X;Li L;Fang Y;Shi W;Li X;Ma H
肝病模型中亮氨酸氨基肽酶的上调首次在体内成像，并使用近红外荧光探针进行成像。
肝脏是一种主要的解毒器官，已经进化出复杂的酶促系统以应对多种病理条件，据报道，亮氨酸氨基肽酶（LAP）参与肝癌细胞中的顺铂的排毒，并有助于固有耐药性。因此，在肝病模型中，膝上活性的体内成像有助于进一步了解膝上在排毒和医学中的功能，但是这种成像方法仍然缺乏。在此，我们为此而开发了一种选择性和敏感的近红外荧光探针（HCAL）。使用探针结合共聚焦荧光成像，我们披露了对乙酰氨基酚诱导的肝损伤和肿瘤小鼠模型中膝上的上调。补充乙酰半胱氨酸可以抑制这种上调，表明膝上的增加可能与生物硫醇缺乏有关。此外，HCAL已被成功地用于肝癌细胞，肿瘤组织和异种移植肿瘤小鼠的模型。这些结果表明，HCAL可能是研究LAP相关肝疾病功能的有前途的工具。
The upregulation of leucine aminopeptidase in hepatopathy models is imaged in vivo for the first time with a near-infrared fluorescent probe. The liver, a main detoxification organ, has evolved a complex enzymatic system to respond to multiple pathological conditions, in which leucine aminopeptidase (LAP) has been reported to participate in detoxifying cisplatin in hepatoma cells and contribute to the intrinsic drug resistance. In vivo imaging of LAP activity in liver disease models is thus helpful to further understand the function of LAP in detoxification and medicine, but such an imaging approach is still lacking. Herein, we develop a selective and sensitive near-infrared fluorescent probe (HCAL) for this purpose. Using the probe, combined with confocal fluorescence imaging, we disclose the upregulations of LAP in acetaminophen-induced liver injury and tumor-bearing mice models. Supplementary acetylcysteine can suppress this upregulation, revealing that the LAP increase may be connected with a deficiency in biothiols. Moreover, HCAL has been used to image LAP in hepatoma cells, tumor tissues and xenograft tumor mice models successfully. These results demonstrate that HCAL may be a promising tool for studying the function of LAP in LAP-associated liver diseases.