Interdisciplinary Graduate School of Agriculture and Engineering, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki, 889-2192, Japan.
Department of Biochemistry and Applied Bioscience, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuenkibanadai-nishi, Miyazaki, 889-2192, Japan.
Dev Comp Immunol. 2021 Feb;115:103894. doi: 10.1016/j.dci.2020.103894. Epub 2020 Oct 17.
ASC is a component of the inflammasome playing crucial roles in the inflammatory response. In mammals, ASC induces pyroptosis and inflammatory cytokine production. In this study, three asc genes (asc1, asc2, and asc3) from the Japanese medaka (Oryzias latipes) were identified and characterized. These asc genes were tandem replicates on chromosome 16, and their exon-intron structures differed between them. All three ASCs conserved the pyrin and caspase-recruitment domains, which are important for inflammasome formation. In phylogenetic analysis, all ASCs clustered with those of other teleosts. The asc1 expression levels were significantly higher in several organs than those of asc2 and asc3, suggesting that asc1 may act as a dominant asc in the Japanese medaka. Expression of the three asc genes showed different patterns during Aeromonas hydrophila and Edwardsiella piscicida infections. Furthermore, their expression was adequately down-regulated in the medaka fin-derived cells stimulated with ATP for 12 h, while asc2 expression was statistically up-regulated after nigericin stimulation for 24 h. Moreover, the expression of asc2 and asc3 was significantly higher in the skin of ASC-1-knockout medaka than in that of the wild type medaka during A. hydrophila infection.
ASC 是炎症小体的一个组成部分，在炎症反应中起着至关重要的作用。在哺乳动物中，ASC 诱导细胞焦亡和炎症细胞因子的产生。在这项研究中，从日本青鳉（Oryzias latipes）中鉴定并表征了三个 asc 基因（asc1、asc2 和 asc3）。这些 asc 基因在染色体 16 上是串联重复的，它们的外显子-内含子结构彼此不同。所有三种 ASC 都保守了吡喃和半胱氨酸蛋白酶募集结构域，这对于炎症小体的形成是重要的。在系统发育分析中，所有的 ASC 都与其他硬骨鱼的 ASC 聚类在一起。asc1 在几个器官中的表达水平明显高于 asc2 和 asc3，这表明 asc1 可能在日本青鳉中作为一个优势 asc 发挥作用。在鳗弧菌和迟钝爱德华氏菌感染期间，三种 asc 基因的表达表现出不同的模式。此外，在 ATP 刺激 12 小时后，它们在青鳉鳍衍生细胞中的表达被充分下调，而在 Nigericin 刺激 24 小时后，asc2 的表达被统计学地上调。此外，在鳗弧菌感染期间，ASC-1 敲除青鳉的皮肤中 asc2 和 asc3 的表达明显高于野生型青鳉。
