Yu Yaoru, Chen Jing, An Lu, Huang Tianci, Wang Wenbo, Cheng Ziqi, Wang Lu, Xu Xuesong, Zhao Zhizhuang, Fu Xueqi, Ma Junfeng
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.
Clinical Laboratory of China-Japan Union Hospital, Jilin University, Changchun, China.
FASEB J. 2023 Apr;37(4):e22844. doi: 10.1096/fj.202202003R.
Phosphatases of regenerating liver (PRLs) are dual-specificity protein phosphatases. The aberrant expression of PRLs threatens human health, but their biological functions and pathogenic mechanisms are unclear yet. Herein, the structure and biological functions of PRLs were investigated using the Caenorhabditis elegans (C. elegans). Structurally, this phosphatase in C. elegans, named PRL-1, consisted of a conserved signature sequence WPD loop and a single C(X) R domain. Besides, by Western blot, immunohistochemistry and immunofluorescence staining, PRL-1 was proved to mainly express in larval stages and express in intestinal tissues. Afterward, by feeding-based RNA-interference method, knockdown of prl-1 prolonged the lifespan of C. elegans but also improved their healthspan, such as locomotion, pharyngeal pumping frequency, and defecation interval time. Furthermore, the above effects of prl-1 appeared to be taken without acting on germline signaling, diet restriction pathway, insulin/insulin-like growth factor 1 signaling pathway, and SIR-2.1 but through a DAF-16-dependent pathway. Moreover, knockdown of prl-1 induced the nuclear translocation of DAF-16, and upregulated the expression of daf-16, sod-3, mtl-1, and ctl-2. Finally, suppression of prl-1 also reduced the ROS. In conclusion, suppression of prl-1 enhanced the lifespan and survival quality of C. elegans, which provides a theoretical basis for the pathogenesis of PRLs in related human diseases.
再生肝脏磷酸酶（PRLs）是双特异性蛋白磷酸酶。PRLs的异常表达威胁人类健康，但其生物学功能和致病机制尚不清楚。在此，利用秀丽隐杆线虫（C. elegans）对PRLs的结构和生物学功能进行了研究。在结构上，秀丽隐杆线虫中的这种磷酸酶名为PRL-1，由一个保守的特征序列WPD环和一个单一的C(X)R结构域组成。此外，通过蛋白质免疫印迹、免疫组织化学和免疫荧光染色，证明PRL-1主要在幼虫阶段表达，并在肠道组织中表达。随后，通过基于喂食的RNA干扰方法，敲低prl-1不仅延长了秀丽隐杆线虫的寿命，还改善了它们的健康状况，如运动能力、咽部抽吸频率和排便间隔时间。此外，prl-1的上述作用似乎不是通过作用于生殖系信号传导、饮食限制途径、胰岛素/胰岛素样生长因子1信号传导途径和SIR-2.1，而是通过一条依赖DAF-16的途径。此外，敲低prl-1诱导了DAF-16的核转位，并上调了daf-16、sod-3、mtl-1和ctl-2的表达。最后，抑制prl-1也降低了活性氧。总之，抑制prl-1提高了秀丽隐杆线虫的寿命和生存质量，这为PRLs在相关人类疾病中的发病机制提供了理论依据。
