ASPP2 attenuates triglycerides to protect against hepatocyte injury by reducing autophagy in a cell and mouse model of non-alcoholic fatty liver disease.
ASPP2 attenuates triglycerides to protect against hepatocyte injury by reducing autophagy in a cell and mouse model of non-alcoholic fatty liver disease.
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ASPP2 通过减少非酒精性脂肪肝细胞和小鼠模型中的自噬来减弱甘油三酯，从而防止肝细胞损伤
DOI：
10.1111/jcmm.12364
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发表时间：
2015-01
影响因子：
5.3
通讯作者：
Meng Q
中科院分区：
文献类型：
--
作者：
Xie F;Jia L;Lin M;Shi Y;Yin J;Liu Y;Chen D;Meng Q
ASPP2是p53结合蛋白家族的促凋亡成员。ASPP2抑制自噬，维持营养缺乏时的能量平衡。我们试图确定ASPP2在非酒精性脂肪性肝病（NAFLD）发病机制中的作用。在NAFLD细胞模型中，对照处理和未处理的HepG2细胞用gfp腺病毒（GFP-ad）预孵育12小时，然后用油酸（OA）处理24小时。实验组用aspp2 -腺病毒（ASPP2-ad）或ASPP2-siRNA预处理HepG2细胞12 h，然后用OA处理24 h。用饲喂蛋氨酸和胆碱缺乏（MCD）的BALB/c小鼠建立NAFLD小鼠模型。对照组脂肪肝小鼠注射GFP-ad预处理10天。在实验组中，用ASPP2-ad预处理的小鼠喂食MCD饮食10天。ASPP2-ad或GFP-ad每5天给药1次。用脂肪肝患者和健康对照者的肝组织分析ASPP2的作用。采用共聚焦荧光显微镜、免疫组织化学、western blot和生化检测检测自噬、凋亡标志物和脂质代谢介质。ASPP2过表达可降低HepG2细胞甘油三酯含量，抑制细胞自噬和凋亡。ASPP2-ad抑制MCD饮食诱导的自噬、脂肪变性和细胞凋亡，并降低先前升高的丙氨酸转氨酶水平。综上所述，ASPP2可能参与非酒精性脂肪性肝炎的脂质代谢，减轻肝衰竭。
ASPP2 is a pro-apoptotic member of the p53 binding protein family. ASPP2 has been shown to inhibit autophagy, which maintains energy balance in nutritional deprivation. We attempted to identify the role of ASPP2 in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In a NAFLD cell model, control treated and untreated HepG2 cells were pre-incubated with GFP-adenovirus (GFP-ad) for 12 hrs and then treated with oleic acid (OA) for 24 hrs. In the experimental groups, the HepG2 cells were pre-treated with ASPP2-adenovirus (ASPP2-ad) or ASPP2-siRNA for 12 hrs and then treated with OA for 24 hrs. BALB/c mice fed a methionine- and choline-deficient (MCD) diet were used to generate a mouse model of NAFLD. The mice with fatty livers in the control group were pre-treated with injections of GFP-ad for 10 days. In the experimental group, the mice that had been pre-treated with ASPP2-ad were fed an MCD diet for 10 days. ASPP2-ad or GFP-ad was administered once every 5 days. Liver tissue from fatty liver patients and healthy controls were used to analyse the role of ASPP2. Autophagy, apoptosis markers and lipid metabolism mediators, were assessed with confocal fluorescence microscopy, immunohistochemistry, western blot and biochemical assays. ASPP2 overexpression decreased the triglyceride content and inhibited autophagy and apoptosis in the HepG2 cells. ASPP2-ad administration suppressed the MCD diet-induced autophagy, steatosis and apoptosis and decreased the previously elevated alanine aminotransferase levels. In conclusion, ASPP2 may participate in the lipid metabolism of non-alcoholic steatohepatitis and attenuate liver failure.
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影响因子：
25.7
作者：
Derdak, Zoltan;Villegas, Kristine A.;Harb, Ragheb;Wu, Annie M.;Sousa, Aryanna;Wands, Jack R.
通讯作者：
Wands, Jack R.
人类脂肪肝病：旧问题和新见解。
DOI：
10.1126/science.1204265
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cohen JC;Horton JD;Hobbs HH
通讯作者：
Hobbs HH
影响因子：
5.3
作者：
Carabelli J;Burgueño AL;Rosselli MS;Gianotti TF;Lago NR;Pirola CJ;Sookoian S
通讯作者：
Sookoian S
影响因子：
3.7
作者：
Cassol E;Misra V;Holman A;Kamat A;Morgello S;Gabuzda D
通讯作者：
Gabuzda D
影响因子：
8.9
作者：
Koo SH
通讯作者：
Koo SH