An identified PfHMGB1 promotes microcystin-LR-induced liver injury of yellow catfish (Pelteobagrus fulvidraco)
An identified PfHMGB1 promotes microcystin-LR-induced liver injury of yellow catfish (Pelteobagrus fulvidraco)
复制标题
已鉴定的 PfHMGB1 促进微囊藻毒素 LR 诱导的黄颡鱼 (Pelteobagrus fulvidraco) 肝损伤
DOI：
10.1016/j.ecoenv.2020.111266
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发表时间：
2021-01-01
影响因子：
6.8
通讯作者：
Fan，Yanru
中科院分区：
文献类型：
--
作者：
Wang，Yun;Xiao，Xiaoxue;Fan，Yanru
微囊藻毒素-LR (MC-LR) 是一种强效肝毒素，可引起肝脏炎症和损伤。然而，相关炎症因子的作用方式尚不完全清楚。 PfHMGB1 是腹腔注射 50 μg/kg MC-LR 的幼年黄颡鱼 (Pelteobagrus fulvidraco) 肝脏中 mRNA 水平诱导的炎症因子。在检查的 11 个组织中，肝脏和肌肉中的 PfHMGB1 mRNA 水平最高。克隆 PfHMGB1 的全长 cDNA 序列并在大肠杆菌中过表达。大肠杆菌，纯化的蛋白质 rPfHMGB1 表现出 DNA 结合亲和力。无内毒素的 rPfHMGB1 (6–150 µg/mL) 也表现出剂量依赖性肝毒性并诱导原代肝细胞炎症基因表达。 PfHMGB1 抗体（抗 PfHMGB1）在体外可降低 MC-LR（30 和 50 μmol/L）诱导的肝毒性，表明 PfHMGB1 在 MC-LR 的毒性作用中起重要作用。体内研究表明 MC-LR 上调肝脏中的 PfHMGB1 蛋白。 MC-LR 暴露后，抗 PfHMGB1 阻断其对应物并降低 ALT/AST 活性。抗 PfHMGB1 部分中和了 MC-LR 诱导的肝细胞解体、细胞核皱缩、线粒体和粗面内质网破坏。这些发现表明 PfHMGB1 促进 MC-LR 诱导的黄颡鱼肝损伤。 HMGB1 可能有助于保护鲶鱼免受广泛的微囊藻毒素污染。
Microcystin-LR (MC-LR) is a potent hepatotoxin that can cause liver inflammation and injury. However, the mode of action of related inflammatory factors is not fully understood. PfHMGB1 is an inflammatory factor induced at the mRNA level in the liver of juvenile yellow catfish (Pelteobagrus fulvidraco) that were intraperitoneally injected with 50 μg/kg MC-LR. ThePfHMGB1mRNA level was highest in the liver and muscle among 11 tissues examined. The full-length cDNA sequence of PfHMGB1 was cloned and overexpressed inE. coli, and the purified protein rPfHMGB1 demonstrated DNA binding affinity. Endotoxin-free rPfHMGB1 (6–150 μg/mL) also showed dose-dependent hepatotoxicity and induced inflammatory gene expression of primary hepatocytes. PfHMGB1 antibody (anti-PfHMGB1)in vitroreduced MC-LR (30 and 50 μmol/L)-induced hepatotoxicity, suggesting PfHMGB1 is important in the toxic effects of MC-LR.In vivostudy showed that MC-LR upregulated PfHMGB1 protein in the liver. The anti-PfHMGB1 blocked its counterpart and reduced ALT/AST activities after MC-LR exposure. Anti-PfHMGB1 partly neutralized MC-LR-induced hepatocyte disorganization, nucleus shrinkage, mitochondria, and rough endoplasmic reticula destruction. These findings suggest that PfHMGB1 promotes MC-LR-induced liver damage in the yellow catfish. HMGB1 may help protect catfish against widespread microcystin pollution.