Diet Supplementation with Soy Protein Isolate, but Not the Isoflavone Genistein, Protects Against Alcohol-Induced Tumor Progression in DEN-Treated Male Mice.
Diet Supplementation with Soy Protein Isolate, but Not the Isoflavone Genistein, Protects Against Alcohol-Induced Tumor Progression in DEN-Treated Male Mice.
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DOI：
10.1007/978-3-319-98788-0_9
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发表时间：
2018
影响因子：
--
通讯作者：
Ronis MJJ
中科院分区：
文献类型：
--
作者：
Mercer KE;Pulliam CF;Hennings L;Cleves MA;Jones EE;Drake RR;Ronis MJJ
本研究将DEN处理的雄性小鼠分为4组：35%高脂酒精液体饲料(Etoh)、以大豆分离蛋白为唯一蛋白质来源的Etoh液体饲料(Etoh/Soy)、添加染料木素的Etoh液体饲料(Etoh/Gen)和饲料组。乙醇饲喂，最终浓度为5%(v/v)，持续16周。正如预期的那样，与喂食组相比，乙醇增加了嗜碱性皮损和腺瘤的发生率和多样性(p<；0.05)。与无水乙醇和无水乙醇/Gen组相比，EtoH/Soy组补充大豆蛋白显著减少腺瘤进展(p<；0.05)。在乙醇饮食中单独补充染料木素没有保护作用。在生理盐水处理的小鼠中，与乙醇处理组相比，大豆喂养显著降低了血清ALT浓度(p<；0.05)，降低了肝脏肿瘤坏死因子α和CD-14的表达，并减少了核转录因子κB蛋白的核积聚(p<；0.05)。关于神经酰胺，高分辨率MALDI-FTICR成像质谱仪显示，与乙醇/大豆组相比，乙醇组中长酰链神经酰胺种类的积累发生了变化，特别是C18。此外，在乙醇/大豆组，酸性神经酰胺酶和鞘氨醇激酶1分别降解神经酰胺为鞘氨醇和将鞘氨醇转化为鞘氨醇-1-磷酸的酶的表达以及鞘氨醇-1-磷酸受体S1PR2和S1PR3的表达均被乙醇上调，而在乙醇/大豆组，p<；0.05。长期饲喂乙醇也增加了肝细胞的增殖和β-连环蛋白靶标的基因表达，包括细胞周期蛋白D1、基质金属蛋白7和谷氨酰胺合成酶，在乙醇/大豆组中这些指标的表达都降低了。这些发现表明，大豆通过减少乙醇诱导的肝损伤所导致的促炎信号，并通过抑制乙醇介导的β-连环蛋白信号来减少肝细胞的增殖，从而预防肿瘤的发生。这些机制可能涉及对鞘脂信号的阻断。
In this study, DEN-treated male mice were assigned to 4 groups: a 35% high fat ethanol liquid diet (EtOH), an EtOH liquid diet with soy protein isolate as the sole protein source (EtOH/SOY) an EtOH liquid diet supplemented with genistein (EtOH/GEN) and a chow group. EtOH feeding, final concentration 5% (v/v), continued for 16 wks. As expected, EtOH increased both the incidence and multiplicity of both basophilic lesions and adenomas compared to the chow fed group, (p<0.05). Soy protein supplementation in the EtOH/SOY group significantly reduced adenoma progression when compared to the EtOH and EtOH/GEN group, (p<0.05). Genistein supplementation alone in the EtOH diet had no protective effect. In saline-treated mice, soy feeding significantly reduced serum ALT concentrations (p<0.05), decreased hepatic TNFα and CD-14 expression and decreased nuclear accumulation of NFκB protein in the EtOH/SOY-treated mice compared to the EtOH group (p<0.05). With respect to ceramides, high resolution MALDI-FTICR Imaging mass spectrometry revealed changes in the accumulation of long acyl chain ceramide species, in particular C18, in the EtOH group when compared to the EtOH/SOY group. Additionally, expression of the enzymes acid ceramidase and sphingosine kinase 1 which degrade ceramide into sphingosine and convert sphingosine to sphingosine-1-phosphate respectively and expression of sphingosine-1-phosphate receptors S1PR2 and S1PR3 were all upregulated by EtOH and suppressed in the EtOH/SOY group, p<0.05. Chronic EtOH feeding also increased hepatocyte proliferation and mRNA expression of β-catenin targets, including cyclin D1, MMP7 and glutamine synthase, which were reduced in the EtOH/SOY group, p<0.05. These findings suggest that soy prevents tumorigenesis by reducing pro-inflammatory signaling resulting from EtOH-induced hepatic injury, and by reducing hepatocyte proliferation through inhibition of EtOH-mediated β-catenin signaling. These mechanisms may involve blockade of sphingolipid signaling.
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影响因子：
4.7
作者：
Su, Ying;Simmen, Rosalia C. M.
通讯作者：
Simmen, Rosalia C. M.
影响因子：
13.5
作者：
Yanagitani, A;Yamada, S;Shiota, G
通讯作者：
Shiota, G
影响因子：
--
作者：
Mercer KE;Hennings L;Ronis MJ
通讯作者：
Ronis MJ
DOI：
10.1080/07315724.2005.10719456
发表时间：
2005-04-01
影响因子：
3.5
作者：
Badger, TM;Ronis, MJJ;Simmen, FA
通讯作者：
Simmen, FA
影响因子：
6
作者：
Bi, Yan;Li, Jiachu;Shah, Vijay
通讯作者：
Shah, Vijay