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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.

Titel:	Icariin induces synoviolin expression through NFE2L1 to protect neurons from ER stress-induced apoptosis.
Autor/in / Beteiligte Person:	Li, F ; Gao, B ; Dong, H ; Shi, J ; Fang, D
Link:	Zum Volltext
Zeitschrift:	PloS one, Jg. 10 (2015-03-25), Heft 3, S. e0119955
Veröffentlichung:	San Francisco, CA : Public Library of Science, 2015
Medientyp:	academicJournal
ISSN:	1932-6203 (electronic)
DOI:	10.1371/journal.pone.0119955
Schlagwort:	Animals Neurons metabolism PC12 Cells Promoter Regions, Genetic Rats Apoptosis drug effects Endoplasmic Reticulum Stress drug effects Flavonoids pharmacology NF-E2-Related Factor 1 metabolism Neurons drug effects Neuroprotective Agents pharmacology Ubiquitin-Protein Ligases metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural Language: English [PLoS One] 2015 Mar 25; Vol. 10 (3), pp. e0119955. <i>Date of Electronic Publication: </i>2015 Mar 25 (<i>Print Publication: </i>2015). MeSH Terms: Apoptosis / drug effects ; Endoplasmic Reticulum Stress / drug effects ; Flavonoids / pharmacology ; NF-E2-Related Factor 1 / metabolism ; Neurons / drug effects ; Neuroprotective Agents / pharmacology ; Ubiquitin-Protein Ligases / *metabolism ; Animals ; Neurons / metabolism ; PC12 Cells ; Promoter Regions, Genetic ; Rats References: Eur J Pharmacol. 2010 Jan 25;626(2-3):213-8. (PMID: 19782061) ; Blood. 2008 Apr 1;111(7):3599-606. (PMID: 18223166) ; EMBO Rep. 2008 May;9(5):480-5. (PMID: 18369366) ; PLoS One. 2014;9(5):e94576. (PMID: 24788773) ; Chin J Integr Med. 2014 Feb;20(2):107-15. (PMID: 24619236) ; Cell Calcium. 2005 Sep-Oct;38(3-4):409-15. 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Icariin induces synoviolin expression through NFE2L1 to protect neurons from ER stress-induced apoptosis.