Zeng Chu, Hou Zhi-Shuai, Zhao Hong-Kui, Xin Yuan-Ru, Liu Meng-Qun, Yang Xiao-Dong, Wen Hai-Shen, Li Ji-Fang
Key Laboratory of Mariculture (Ocean University of China), Ministry of Education (KLMME), Ocean University of China, Qingdao, China.
Key Laboratory of Mariculture (Ocean University of China), Ministry of Education (KLMME), Ocean University of China, Qingdao, China.
Dev Comp Immunol. 2021 May;118:103987. doi: 10.1016/j.dci.2020.103987. Epub 2020 Dec 24.
Caspases are highly conserved cysteine-dependent aspartyl-specific proteases that play an important role in regulating cell death and inflammation. However, the caspase genes have not been systematically studied in rainbow trout (Oncorhynchus mykiss). Rainbow trout experienced 4 rounds (4R) of genome duplication in the evolutionary history. Thereby an increased numbers of paralogs are observed in trout, probably with more complicated gene functions. We identified 18 caspase genes in rainbow trout, including two inflammatory caspases (casp1a, casp1b), six apoptosis executioner caspases (casp3, casp3a1, casp3a2, casp3b, casp6, and casp7), nine apoptosis initiator caspases (casp2a, casp2b, casp8, casp9a, casp9b, casp10a, casp10b, casp20a, and casp20b) and one uncategorized caspase gene (casp17). To investigate the potentially physiological functions of caspase genes, we challenged the rainbow trout with Aeromonas salmonicida (A. salmonicida) and Vibrio anguillarum (V. anguillarum). Results showed that the CASP3-regulated intrinsic apoptosis was activated after A. salmonicida infection, while the CASP8 and CASP6-regulated extrinsic apoptosis exerted the greatest effect on trout challenged with V. anguillarum. In response to V. anguillarum infection, the data of RNA-Seq further showed the casp8 was tightly integrated with the significantly enriched Gene Ontology terms and functional pathways, including apoptosis regulation, pathogen detection and immunomodulation. Our study provides a foundation for the physiological functions and regulatory network of the caspase genes in teleosts.
半胱天冬酶是高度保守的、依赖半胱氨酸的天冬氨酸特异性蛋白酶，在调节细胞死亡和炎症中发挥重要作用。然而，半胱天冬酶基因尚未在虹鳟（Oncorhynchus mykiss）中得到系统研究。虹鳟在进化史上经历了4轮（4R）基因组复制。因此，在鳟鱼中观察到旁系同源基因数量增加，其基因功能可能更复杂。我们在虹鳟中鉴定出18个半胱天冬酶基因，包括两个炎症性半胱天冬酶（casp1a、casp1b）、六个凋亡执行半胱天冬酶（casp3、casp3a1、casp3a2、casp3b、casp6和casp7）、九个凋亡起始半胱天冬酶（casp2a、casp2b、casp8、casp9a、casp9b、casp10a、casp10b、casp20a和casp20b）以及一个未分类的半胱天冬酶基因（casp17）。为了研究半胱天冬酶基因潜在的生理功能，我们用杀鲑气单胞菌（A. salmonicida）和鳗弧菌（V. anguillarum）感染虹鳟。结果表明，杀鲑气单胞菌感染后激活了由CASP3调节的内源性凋亡，而由CASP8和CASP6调节的外源性凋亡在鳗弧菌感染的鳟鱼中作用最大。针对鳗弧菌感染，RNA测序数据进一步表明，casp8与显著富集的基因本体术语和功能途径紧密相关，包括凋亡调节、病原体检测和免疫调节。我们的研究为硬骨鱼类半胱天冬酶基因的生理功能和调控网络提供了基础。
