17β-Estradiol attenuates saturated fatty acid diet-induced liver injury in ovariectomized mice by up-regulating hepatic senescence marker protein-30

被引:22
作者
Fukui, Michiaki [1 ]
Senmaru, Takafumi
Hasegawa, Goji
Yamazaki, Masahiro
Asano, Mai
Kagami, Yayoi [4 ]
Ishigami, Akihito [4 ]
Maruyama, Naoki [4 ]
Iwasa, Koichi [2 ]
Kitawaki, Jo [2 ]
Itoh, Yoshito [3 ]
Okanoue, Takeshi [5 ]
Ohta, Mitsuhiro [6 ]
Obayashi, Hiroshi [7 ]
Nakamura, Naoto
机构
[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Endocrinol & Metab, Kamikyo Ku, Kyoto 6028566, Japan
[2] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Obstet & Gynecol, Kyoto 6028566, Japan
[3] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Mol Gastroenterol & Hepatol, Kyoto 6028566, Japan
[4] Tokyo Metropolitan Inst Gerontol, Tokyo, Japan
[5] Saiseikai Salta Hosp, Dept Gastroenterol & Hepatol, Osaka, Japan
[6] Kobe Pharmaceut Univ, Dept Med Biochem, Kobe, Hyogo 658, Japan
[7] Inst Bioresponse Informat, Kyoto, Japan
基金
日本学术振兴会;
关键词
Senescence marker protein-30; 17; beta-Estradiol; Endoplasmic reticulum stress; Apoptosis; Saturated fatty acids; Nonalcoholic steatohepatitis; ENDOPLASMIC-RETICULUM STRESS; TERM EZETIMIBE THERAPY; INDUCED APOPTOSIS; GENE-EXPRESSION; DISEASE; SMP30; STEATOSIS; CALCIUM; ALPHA; CELLS;
D O I
10.1016/j.bbrc.2011.10.025
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
Senescence marker protein-30 (SMP30) plays an important role in intracellular Ca2+ homeostasis. The aim of the present study was to investigate the effects of estrogens on liver apoptotic damage and changes in SMP30 expression induced by a high saturated fatty acid diet (HSFD). Ovariectomized mice (OVX) and sham-operated mice (SHAM) were randomly divided into five groups: SHAM fed a normal diet (SHAM/ND). SHAM fed HSFD (SHAM/HSFD), OVX fed ND (OVX/ND), OVX fed HSFD (OVX/HSFD) and OVX fed HSFD with 17 beta-estradiol (E2) supplementation using an implanted slow-release pellet (OVX/ HSFD + E2). After 8 weeks, markers of endoplasmic reticulum (ER) stress and apoptosis, and levels of tumor necrosis factor-alpha (TNF alpha and SMP30 expression were investigated. Compared with SHAM/ND, OVX/HSFD mice showed significantly increased spliced X-box protein-1 (s-XBP1), phosphorylated eukaryotic initiation factor-2 alpha (p-eIF2 alpha), glucose-regulated protein 78 (GPR78), C/EBP homologous protein (CHOP), cytosolic cytochrome c, caspase-3 activity, and TNF alpha, and significantly decreased SMP30. These differences in OVX/HSFD mice were restored to the levels of SHAM/ND mice by E2 supplementation. These results suggest that E2 supplementation attenuates HSFD-induced liver apoptotic death in ovariectomized mice by up-regulating SMP30. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:252 / 257
页数:6
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