title: Increased expression of ERp57/GRP58 is protective against pancreatic beta cell death caused by autophagic failure.
abstract: Autophagy is a tightly regulated self-digestion system. As in other cell types, autophagy plays an essential role in the homeostasis of pancreatic beta cells. However, the mechanisms involved in the deterioration of beta cell function caused by autophagic failure have not yet been fully elucidated. To gain insight into its mechanisms, we compared the protein expression of islets from beta cell-specific Atg7-deficient mice (Atg7(Δβ-cell) mice) and their controls (Atg7(f/f) mice). Liquid chromatography/mass spectrometry after 1-dimensional electrophoresis identified the increased expression of ERp57/GRP58 in islets isolated from Atg7(Δβ-cell) mice compared with those from Atg7(f/f) mice. The expression level of ERp57 was also elevated in rat insulinoma INS-1 cells by inducible knock-down of the atg7-gene. In Atg7 knock-down INS-1 cells, the suppression of ERp57 expression by siRNA resulted in an increase in the level of cleaved Caspase-3 protein and a decrease in the number of live cells. Furthermore, cell cycle analyses demonstrated that the suppressed expression of ERp57 increased the sub-G1 population. These data reveal that increased expression of ERp57 may contribute to the protection from beta cell death caused by autophagic failure.
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: uchitoyo@juntendo.ac.jp.
authors.forename: Toyoyoshi
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Abe
authors.affiliation: Division of Proteomics and BioMolecular Science, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Hikari
authors.initials: H
authors.lastname: Taka
authors.affiliation: Division of Proteomics and BioMolecular Science, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Komiya
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Hara
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogihara
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Center for Therapeutic Innovations in Diabetes, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; JST-CREST Program, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.affiliation: Division of Proteomics and BioMolecular Science, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Center for Therapeutic Innovations in Diabetes, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Center for Molecular Diabetology, Juntendo University, Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: hwatada@juntendo.ac.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D055785:Gene Knockdown Techniques; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C502661:Atg7 protein, mouse; C561242:Atg7 protein, rat; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C513196:PDIA3 protein, rat; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes
keywords: Apoptosis; Autophagy; ERp57; Pancreatic beta cells