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来自红鳍东方鲀的 CIRBP 的分子特征及其在冷诱导肝损伤中的潜在作用。

Molecular characterization of CIRBP from Takifugu fasciatus and its potential roles in cold-induced liver damage.

机构信息

College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing 210023, China.

College of Marine Science and Engineering, Nanjing Normal University, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing 210023, China; Co-Innovation Center for Marine Bio-Industry Technology, Lian Yungang, Jiangsu 222005, China.

出版信息

Int J Biol Macromol. 2024 Nov;281(Pt 2):136492. doi: 10.1016/j.ijbiomac.2024.136492. Epub 2024 Oct 10.

Abstract

As a potent stressor, environmental cold stress induces severe mitochondrial dysfunction with the overproduction of reactive oxygen species (ROS) in fish, resulting in liver damage. However, the molecular mechanisms underlying the cold-induced liver damage remain unclear. In the present study, the cold-inducible RNA-binding protein (CIRBP) from Takifugu fasciatus was characterized, and its role in cold-induced oxidative stress damage was investigated. An acute liver injury model was constructed by exposing T. fasciatus individuals to temperatures of 25, 19, and 13 °C. Cold exposure markedly induced histomorphological liver injury and triggered endogenous apoptosis and NLRP3 inflammatory response. Cold treatment significantly increased CIRBP gene expression. A similar expression pattern was detected for thioredoxin (TRX), suggesting that these two proteins play a role in the establishment of cold adaptation. CIRBP binds directly to the 3'-UTR of TRX. Furthermore, in vivo experiment showed that, when CIRBP expression in T. fasciatus is knocked down, the time to loss equilibrium significantly shortened at 13 °C. Taken together, our study revealed that CIRBP is a critical protective factor against cold induced liver damage and that the CIRBP/TRX pathway could function as an underlying mechanism for cold adaptation in teleosts.

摘要

作为一种强烈的应激源,环境冷应激会导致鱼类线粒体功能严重障碍,活性氧(ROS)产生过多,从而导致肝损伤。然而,冷诱导肝损伤的分子机制尚不清楚。本研究对来自红鳍东方鲀的冷诱导 RNA 结合蛋白(CIRBP)进行了表征,并研究了其在冷诱导氧化应激损伤中的作用。通过将红鳍东方鲀个体暴露于 25、19 和 13°C 的温度下,构建了急性肝损伤模型。冷暴露显著诱导了组织形态学肝损伤,并引发了内源性细胞凋亡和 NLRP3 炎症反应。冷处理显著增加了 CIRBP 基因的表达。硫氧还蛋白(TRX)的表达模式也相似,表明这两种蛋白在冷适应的建立中发挥作用。CIRBP 直接结合 TRX 的 3'-UTR。此外,体内实验表明,当红鳍东方鲀中的 CIRBP 表达被敲低时,在 13°C 下失去平衡的时间明显缩短。综上所述,本研究表明 CIRBP 是一种对抗冷诱导肝损伤的关键保护因子,CIRBP/TRX 途径可能是硬骨鱼类冷适应的潜在机制。

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