title: Naringenin inhibits the aggregation of expanded polyglutamine tract-containing protein through the induction of endoplasmic reticulum chaperone GRP78.
abstract: Polyglutamine (polyQ) diseases are inherited neurodegenerative diseases characterized by the aggregation of proteins containing expanded polyQ tract. Recently, we have shown that GRP78, the endoplasmic reticulum (ER) chaperone, was significantly decreased in the cells expressing enhanced green fluorescent protein with a pathological-length polyQ tract (EGFP-polyQ97), but not with a non-pathological-length polyQ tract (EGFP-polyQ24), and the expression levels of GRP78 were inversely related to the aggregation of EGFP-polyQ97. In this study, we performed the screening for compounds that modulate the GRP78 expression in herbal medicines, and found that naringenin, one of the major constitutions of Kanzo (Glycyrrhizae Radix), induced the expression of GRP78 in several mammalian cells. Furthermore, naringenin suppressed the protein aggregation caused by EGFP-polyQ97 in mammalian cells. These findings suggested that naringenin seemed to be a new inducer of GRP78 in mammalian cells, and may be a potential therapeutic agent for diseases caused by ER stress such as polyQ diseases.
authors.affiliation: Department of Biochemistry & Molecular Biology, Division of Biological Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. yamagishi@mb.kyoto-phu.ac.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamagishi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Chika
authors.initials: C
authors.lastname: Noda
authors.forename: Takumi
authors.initials: T
authors.lastname: Hatayama
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D044950:Flavanones / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010455:Peptides / Q000378:metabolism*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D044950:Flavanones; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D010455:Peptides; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C097188:polyglutamine; C005273:naringenin