期刊
REDOX BIOLOGY
卷 54, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2022.102383
关键词
Long noncoding RNA; MAGI2-AS3; HSPA8; Cell senescence
资金
- National Key RD Program [2017YFA0504000]
- National Natural Science Foundation of China [91849203, 31900893]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB39000000]
The downregulation of MAGI2-AS3 decreases superoxide levels and hydrogen peroxide content by stabilizing the HSPA8 protein level, leading to delayed cell senescence through the suppression of the ROS/MAP2K6/p38 signaling pathway. These findings suggest a potential anti-aging application.
The redox homeostasis system regulates many biological processes, intracellular antioxidant production and redox signaling. However, long noncoding RNAs (lncRNAs) involved in redox regulation have rarely been reported. Herein, we reported that downregulation of MAGI2-AS3 decreased the superoxide level in Human fibroblasts (Fbs), a replicative aging model, as detected by the fluorescent probes dihydroethidium (DHE) and MitoSOX (TM) Red. RNA pulldown combined with mass spectrometry showed that HSPA8 is a novel interacting protein of MAGI2-AS3, which was further confirmed by photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP). Downregulation of MAGI2-AS3 decreased the hydrogen peroxide (H2O2) content by stabilizing the HSPA8 protein level via inhibiting the protesome degradation of HSPA8. Further evidence showed that MAGI2-AS3 interacted with the C-terminal domain (CTD) of HSPA8. Downregulation of MAGI2-AS3 delayed cell senescence, while this antiaging effect was abolished by HSPA8 knockdown. The underlying molecular mechanism by which MAGI2-AS3 knockdown inhibited cell senescence was mediated via suppression of the ROS/MAP2K6/p38 signaling pathway. Taken together, these findings revealed that dow-nregulation of lncRNA MAGI2-AS3 decreased the H2O2 content and delayed cell senescence by stabilizing the HSPA8 protein level, identifying a potential antiaging application.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据