Icariin induces Synoviolin expression through NFE2L1 to protect neurons from ER stress-induced apoptosis

Fei Li, Beixue Gao, Hongxin Dong, Jingshan Shi, Deyu Fang

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Abstract

By suppressing neuronal apoptosis, Icariin is a potential therapeutic drug for neuronal degenerative diseases. The molecular mechanisms of Icariin anti-apoptotic functions are still largely unclear. In this report, we found that Icariin induces the expression of Synoviolin, an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis. The nuclear factor erythroid 2-related factor 1 (NFE2L1) is responsible for Icariin-mediated Synoviolin gene expression. Mutation of the NFE2L1-binding sites in a distal region of the Synoviolin promoter abolished Icariin-induced Synoviolin promoter activity, and knockdown of NFE2L1 expression prevented Icariin-stimulated Synoviolin expression. More importantly, Icariin protected ER stress-induced apoptosis of PC12 cells in a Synoviolin-dependent manner. Therefore, our study reveals Icariin-induced Synoviolin expression through NFE2L1 as a previously unappreciated molecular mechanism underlying the neuronal protective function of Icariin.

Original languageEnglish (US)
Article numbere0119955
JournalPloS one
Volume10
Issue number3
DOIs
StatePublished - Mar 25 2015

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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