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2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (Danio rerio)
Toxins ( IF 3.9 ) Pub Date : 2021-11-22 , DOI: 10.3390/toxins13110826
Dan Li 1 , Zhi Li 1 , Tianchang Zhang 1 , Bo Peng 1 , Yan Zhang 1 , Hongwen Sun 2 , Shuo Wang 1
Affiliation  

It is important to note that 2-Amino-3-methylimidazole[4,5-f]quinoline (IQ) is one of the most common heterocyclic amines (HCAs), which is a class of mutagenic/carcinogenic harmful compounds mainly found in high-protein thermal processed foods and contaminated environments. However, the pre-carcinogenic toxicity of IQ to the liver and its mechanism are poorly understood, further research is needed. In light of this, we exposed zebrafish to IQ (0, 8, 80, and 800 ng/mL) for 35 days, followed by comprehensive experimental studies. Histopathological and ultrastructural analysis showed that hepatocytes were damaged. TUNEL results showed that IQ induced apoptosis of liver cells, the expression of apoptosis factor gene was significantly increased, and the expression of Bcl-2 protein was significantly decreased. In addition, upregulated expression of the 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) and endoplasmic reticulum stress (ERS)-related factors transcription levels were elevated obviously, suggesting that IQ induced ERS. Decreased protein expression of autophagy-related 5 (Atg5)-Atg12, Beclin1, and LC3-II, increased protein expression of p62, and autophagy-related factors transcription levels were significantly decreased, suggesting that IQ inhibited autophagy. Overall, our research showed that the potential harm of IQ to the liver before the occurrence of liver cancer was related to ERS and its mediated autophagy and apoptosis pathways.

中文翻译:

2-氨基-3-甲基咪唑并[4,5-f]喹啉通过抑制斑马鱼自噬和诱导内质网应激触发肝损伤(斑马鱼)

需要注意的是,2-氨基-3-甲基咪唑[4,5-f]喹啉(IQ)是最常见的杂环胺(HCA)之一,是一类致突变/致癌的有害化合物,主要存在于高-蛋白质热加工食品和受污染的环境。然而,IQ对肝脏的致癌前毒性及其机制尚不清楚,需要进一步研究。有鉴于此,我们将斑马鱼暴露在 IQ(0、8、80 和 800 ng/mL)中 35 天,然后进行全面的实验研究。组织病理学和超微结构分析显示肝细胞受损。TUNEL结果显示IQ诱导肝细胞凋亡,凋亡因子基因表达显着升高,Bcl-2蛋白表达显着降低。此外,78-kDa葡萄糖调节蛋白(GRP78)和C/EBP同源蛋白(CHOP)表达上调,内质网应激(ERS)相关因子转录水平明显升高,提示IQ诱导了ERS。自噬相关5(Atg5)-Atg12、Beclin1和LC3-II蛋白表达降低,p62蛋白表达增加,自噬相关因子转录水平显着降低,提示IQ抑制自噬。总体而言,我们的研究表明,在肝癌发生之前,IQ对肝脏的潜在危害与ERS及其介导的自噬和凋亡通路有关。表明智商诱导了ERS。自噬相关5(Atg5)-Atg12、Beclin1和LC3-II蛋白表达降低,p62蛋白表达增加,自噬相关因子转录水平显着降低,提示IQ抑制自噬。总体而言,我们的研究表明,在肝癌发生之前,IQ对肝脏的潜在危害与ERS及其介导的自噬和凋亡通路有关。表明智商诱导了ERS。自噬相关5(Atg5)-Atg12、Beclin1和LC3-II蛋白表达降低,p62蛋白表达增加,自噬相关因子转录水平显着降低,提示IQ抑制自噬。总体而言,我们的研究表明,在肝癌发生之前,IQ对肝脏的潜在危害与ERS及其介导的自噬和凋亡通路有关。
更新日期:2021-11-22
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