title: Methionine sulfoxide reductase B3 protects from endoplasmic reticulum stress in Drosophila and in mammalian cells.
abstract: Methionine sulfoxide reductase B3A (MsrB3A), which catalyzes the stereospecific reduction of methionine-R-sulfoxide to methionine, is localized to the endoplasmic reticulum (ER). Here, we report a critical role of the ER-targeted MsrB3 in protection against ER stress in Drosophila and in mammalian cells. Flies overexpressing human MsrB3A exhibited significantly increased resistance to ER stress induced by dithiothreitol. These flies also showed slightly enhanced resistance to tunicamycin-induced ER stress. In addition, overexpression of MsrB3A in mammalian cells increased resistance to dithiothreitol- and thapsigargin-induced ER stresses. However, MsrB3A overexpression had no effect on the resistance to tunicamycin-induced ER stress. Knockdown of MsrB3A in mammalian cells led to a significant decrease in the resistance to thapsigargin-induced ER stress, but had no effects on the resistance to either dithiothreitol- or tunicamycin-induced ER stress. Collectively, our data provide evidence that the ER-type of MsrB3 plays an important role in protection against ER stress, suggesting that MsrB3 may be involved in the regulation of ER homeostasis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu 705-717, Republic of Korea.
authors.forename: Geun-Hee
authors.initials: GH
authors.lastname: Kwak
authors.forename: Do-Hwan
authors.initials: DH
authors.lastname: Lim
authors.forename: Jee Yun
authors.initials: JY
authors.lastname: Han
authors.forename: Young Sik
authors.initials: YS
authors.lastname: Lee
authors.forename: Hwa-Young
authors.initials: HY
authors.lastname: Kim
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D015536:Down-Regulation; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D051150:Methionine Sulfoxide Reductases / Q000235:genetics / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D019284:Thapsigargin; D051150:Methionine Sulfoxide Reductases; C524352:MSRB3 protein, human