TY - JOUR
T1 - Icariin induces Synoviolin expression through NFE2L1 to protect neurons from ER stress-induced apoptosis
AU - Li, Fei
AU - Gao, Beixue
AU - Dong, Hongxin
AU - Shi, Jingshan
AU - Fang, Deyu
N1 - Publisher Copyright:
© 2015 Li et al.
PY - 2015/3/25
Y1 - 2015/3/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84926657720&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926657720&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0119955
DO - 10.1371/journal.pone.0119955
M3 - Article
C2 - 25806530
AN - SCOPUS:84926657720
SN - 1932-6203
VL - 10
JO - PLoS One
JF - PLoS One
IS - 3
M1 - e0119955
ER -