title: Icariin induces synoviolin expression through NFE2L1 to protect neurons from ER stress-induced apoptosis.
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.
authors: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College, Zunyi, China; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave, Chicago, IL, 60611, United States of America.
authors: Fei
authors: F
authors: Li
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave, Chicago, IL, 60611, United States of America.
authors: Beixue
authors: B
authors: Gao
authors: Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave, Chicago, IL, 60611, United States of America.
authors: Hongxin
authors: H
authors: Dong
authors: Department of Pharmacology and the Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical College, Zunyi, China.
authors: Jingshan
authors: J
authors: Shi
authors: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave, Chicago, IL, 60611, United States of America.
authors: Deyu
authors: D
authors: Fang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D051265:NF-E2-Related Factor 1 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D051381:Rats; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D051265:NF-E2-Related Factor 1; D018696:Neuroprotective Agents; C544172:Syvn1 protein, rat; D044767:Ubiquitin-Protein Ligases; C056599:icariin