PMID- 30471861 OWN - NLM STAT- MEDLINE DCOM- 20190603 LR - 20190603 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 508 IP - 1 DP - 2019 Jan 1 TI - Identification of WWP1 as an obesity-associated E3 ubiquitin ligase with a protective role against oxidative stress in adipocytes. PG - 117-122 LID - S0006-291X(18)32560-9 [pii] LID - 10.1016/j.bbrc.2018.11.127 [doi] AB - White adipose tissue (WAT) is not only the main tissue for energy storage but also an endocrine organ that secretes adipokines. Obesity is the most common metabolic disorder and is related to alterations in WAT characteristics, such as chronic inflammation and increasing oxidative stress. WW domain containing E3 ubiquitin protein ligase 1 (WWP1) is a HECT-type ubiquitin E3 ligase that has been implicated in various pathologies. In the present study, we found that WWP1 was upregulated in obese WAT in a p53-dependent manner. To investigate the functions of WWP1 in adipocytes, a proteome analysis of WWP1 overexpression (OE) and knockdown (KD) 3T3-L1 cells was performed. This analysis showed a positive correlation between WWP1 expression and the abundance of several antioxidative proteins. Thus, we measured reactive oxygen species (ROS) in WWP1 OE and KD cells. Consistent with the proteome results, WWP1 OE reduced ROS levels, whereas KD increased them. These findings indicate that WWP1 is an obesity-inducible E3 ubiquitin ligase that can protect against obesity-associated oxidative stress in WAT. CI - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Kobayashi, Masaki AU - Kobayashi M AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Hoshino, Shunsuke AU - Hoshino S AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Abe, Takuro AU - Abe T AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Okita, Naoyuki AU - Okita N AD - Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Division of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, 1-1-1 Daigakudori, Sanyo-onoda, Yamaguchi, 756-0884, Japan. FAU - Tagawa, Ryoma AU - Tagawa R AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Nagai, Wataru AU - Nagai W AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Konno, Ryutaro AU - Konno R AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Suzuki, Yuki AU - Suzuki Y AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Furuya, Kazuhiro AU - Furuya K AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Ishikawa, Natsumi AU - Ishikawa N AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Okado, Hitoshi AU - Okado H AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Oku, Misako AU - Oku M AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Iwamoto, Machiko AU - Iwamoto M AD - Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan. FAU - Miura, Yuri AU - Miura Y AD - Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan. FAU - Sudo, Yuka AU - Sudo Y AD - Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. FAU - Higami, Yoshikazu AU - Higami Y AD - Laboratory of Molecular Pathology & Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. Electronic address: higami@rs.noda.tus.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181122 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Proteome) RN - 0 (RNA, Messenger) RN - EC 2.3.2.26 (WWP1 protein, mouse) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/*metabolism MH - Adipose Tissue, White/metabolism MH - Animals MH - Diet, High-Fat/adverse effects MH - Disease Models, Animal MH - Gene Knockdown Techniques MH - Genes, p53 MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Obesity/etiology/genetics/metabolism MH - Oxidative Stress MH - Proteome/genetics/metabolism MH - RNA, Messenger/genetics/metabolism MH - Ubiquitin-Protein Ligases/antagonists & inhibitors/genetics/*metabolism MH - Up-Regulation OTO - NOTNLM OT - Obesity OT - Oxidative stress OT - WWP1 OT - White adipose tissue EDAT- 2018/11/26 06:00 MHDA- 2019/06/04 06:00 CRDT- 2018/11/26 06:00 PHST- 2018/11/05 00:00 [received] PHST- 2018/11/20 00:00 [accepted] PHST- 2018/11/26 06:00 [pubmed] PHST- 2019/06/04 06:00 [medline] PHST- 2018/11/26 06:00 [entrez] AID - S0006-291X(18)32560-9 [pii] AID - 10.1016/j.bbrc.2018.11.127 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2019 Jan 1;508(1):117-122. doi: 10.1016/j.bbrc.2018.11.127. Epub 2018 Nov 22.