Identification of WWP1 as an obesity-associated E3 ubiquitin ligase with a protective role against oxidative stress in adipocytes

被引：13

作者：

Kobayashi, Masaki ^{[1
,2
]}

Hoshino, Shunsuke ^{[1
,2
]}

Abe, Takuro ^{[1
]}

Okita, Naoyuki ^{[2
,3
]}

Tagawa, Ryoma ^{[1
]}

Nagai, Wataru ^{[1
]}

Konno, Ryutaro ^{[1
]}

Suzuki, Yuki ^{[1
]}

Furuya, Kazuhiro ^{[1
]}

Ishikawa, Natsumi ^{[1
]}

Okado, Hitoshi ^{[1
]}

Oku, Misako ^{[1
]}

Iwamoto, Machiko ^{[4
]}

Miura, Yuri ^{[4
]}

Sudo, Yuka ^{[2
]}

Higami, Yoshikazu ^{[1
,2
]}

机构：

[1] Tokyo Univ Sci, Lab Mol Pathol & Metab Dis, Fac Pharmaceut Sci, 2641 Yamazaki, Noda, Chiba 2788510, Japan

[2] Tokyo Univ Sci, Translat Res Ctr, Res Inst Sci & Technol, 2641 Yamazaki, Noda, Chiba 2788510, Japan

[3] Sanyo Onoda City Univ, Div Pathol Biochem, Fac Pharmaceut Sci, 1-1-1 Daigakudori, Yamaguchi 7560884, Japan

[4] Tokyo Metropolitan Inst Gerontol, Itabashi Ku, 35-2 Sakae Cho, Tokyo 1730015, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2019年 / 508卷 / 01期

基金：

日本学术振兴会;

关键词：

White adipose tissue; Obesity; WWP1; Oxidative stress; INSULIN-RESISTANCE; ADIPOSE-TISSUE; TARGETS; DEGRADATION; RECEPTOR; EXPRESSION; EMISSION; RUNX2;

D O I：

10.1016/j.bbrc.2018.11.127

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2018 The Authors. Published by Elsevier Inc.

引用

页码：117 / 122

页数：6

共 33 条

[1] Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans [J].