1-苯基2-硫脲通过p53调控自噬活性来保护斑马鱼神经丘毛细胞  

1-Phenyl 2-Thiourea Protects Hair Cells in Zebrafish Neuromast by Regulating Autophagy Through p53

作　　者：秦彦筠 范纯新[1,2] 王建[1,2] Qin Yanjun;Fan Chunxin;Wang Jian(International Research Center for Marine Biosciences,Ministry of Science and Technology,Shanghai Ocean University,Shanghai 201306,China;Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources,Shanghai Ocean University,Ministry of Education,Shanghai 201306,China)

机构地区：[1]上海海洋大学国家海洋生物科学国际联合研究中心,上海201306 [2]上海海洋大学水产种质资源发掘与利用教育部重点实验室,上海201306

出　　处：《中国海洋大学学报（自然科学版）》2024年第1期79-85,共7页Periodical of Ocean University of China

基　　金：国家自然科学基金面上项目(31772406)资助。

摘　　要：为了确定细胞自噬与毛细胞存活的关系,通过溶酶体标记物Lyso Tracker对神经丘的细胞自噬进行活体染色发现,斑马鱼(Danio rerio)经过苯基硫脲(PTU)处理后,其神经丘毛细胞Lyso Tracker信号强度增加,并伴随毛细胞数量增多和肿瘤抑制蛋白p53基因(Tumor protein p53 gene,tp53)上调。为了阐明毛细胞的存活和保护机制,通过CRISPR/Cas9技术构建了tp53突变体斑马鱼,发现该基因突变后不会影响斑马鱼神经丘毛细胞的数量,但抑制了PTU对神经丘毛细胞自噬的促进,神经丘毛细胞不再增多。研究结果表明:PTU可以通过上调tp53基因的表达,促进斑马鱼侧线神经丘毛细胞的自噬活性,进而促进毛细胞的存活,为保护毛细胞奠定了重要基础。To illustrate the relationship between autophagy and hair cell survival,we labeled the neuromast in zebrafish with Lyso Tracker to track the autophagy in vivo.We found that 1-phenyl 2-thiourea(PTU)treatment induced the Lyso Tracker signaling enhancement in hair cells specifically,and also resulted in an increase in the number of hair cells and the expression of tp53 gene.To clarify the survival and protection mechanisms of hair cells,we constructed the tp53 mutant zebrafish by CRISPR/Cas9 technology.The tp53 mutation did not affect the number of hair cells in neuromast.However,the tp53 mutation reduced the enhancement of autophagy in hair cell induced by PTU,and lowered the number of hair cells increased by PTU treatment.Our evidence shows that PTU can promote autophagy in hair cells of lateral line neuromast in zebrafish by upregulating the expression of tp53 gene,thereby promoting the survival of hair cells,laying an important foundation for hair cell protection.

关 键 词：tp53基因 侧线系统 毛细胞 细胞自噬 苯基硫脲 

分 类 号：S917[农业科学—水产科学]