2015年第42卷第10期目录
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封面故事:UBXD8 (ubiquitin regulatory X domain-containing protein 8)是能与p97/VCP相互作用共同参与内质网相关的泛素化后蛋白降解过程的膜蛋白.研究表明UBXD8能够定位到脂滴上,同时调控甘油三酯的代谢.邹飞等以小鼠成骨骼肌细胞C2C12为模型,采用改良的CRISPR/Cas9技术敲除C2C12细胞中UBXD8.研究表明,敲除UBXD8没有显著改变脂滴上蛋白质的分布,但增加了细胞内中性脂的累积,此外敲除UBXD8可缓解棕榈酸引起的胰岛素抵抗并抵抗其引起的细胞凋亡.当在UBXD8敲除的细胞中重新过表达UBXD8后,细胞再次出现了棕榈酸引起的胰岛素抵抗及细胞凋亡.综上,UBXD8在细胞脂质代谢及其异常所引起的胰岛素信号和细胞凋亡中起着十分重要的作用.
(邹 飞,刁志清,张红超,徐式孟,刘平生,梁 斌,魏 璇. 骨骼肌细胞中UBXD8的敲除及其对脂质代谢的影响,本期第926~934页)
Cover Story:UBXD8 is a membrane protein that mediates endoplasmic reticulum-associated protein ubiquitination and degradation by interacting with p97/VCP. Recently, lipid droplet proteomic studies show the lipid droplet localization of UBXD8. Besides, UBXD8 is also involved in triglyceride metabolism. However, the molecular mechanism by which UBXD8 regulates triglyceride metabolism is still obscure. Here we knocked out UBXD8 in mouse C2C12 myoblasts by CRISPR/Cas9. We selected 2 UBXD8 knockout (KO) clone cell lines from 26 possible KO clones. UBXD8 KO did not change the lipid droplet proteins expression pattern. However, UBXD8 KO led to the accumulation of neutral lipid. Furthermore, our data show that UBXD8 KO could alleviate palmitate-induced insulin resistance and rescue palmitate-induced apoptosis which was characterized by PARP splicing. In addition, the phenotype of palmitate-induced insulin resistance and apoptosis was reappeared after overexpressing UBXD8 in UBXD8 KO cells. These data suggested that UBXD8 plays an important role in lipid metabolism and its abnormity related insulin signal and apoptosis.
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