Ethanol Enhances TGF-β Activity by Recruiting TGF-β Receptors From Intracellular Vesicles/Lipid Rafts/Caveolae to Non-Lipid Raft Microdomains.
Ethanol Enhances TGF-β Activity by Recruiting TGF-β Receptors From Intracellular Vesicles/Lipid Rafts/Caveolae to Non-Lipid Raft Microdomains.
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DOI：
10.1002/jcb.25389
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发表时间：
2016-04
影响因子：
4
通讯作者：
Huang JS
中科院分区：
文献类型：
--
作者：
Huang SS;Chen CL;Huang FW;Johnson FE;Huang JS
定期饮用适量乙醇对动脉粥样硬化性心血管疾病（ASCVD）有重要的健康益处。过度放纵会导致许多疾病，尤其是酒精性肝病（ALD）。乙醇对人类健康产生有益和有害影响的机制尚不清楚。本研究表明，在稳定表达含有smad2依赖元件的荧光素酶报告基因的Mv1Lu细胞中，乙醇可提高TGF-β刺激的荧光素酶活性，最大可提高0.5-1% （v/v）。在Mv1Lu细胞中，0.5%乙醇使P-Smad2（一种典型的TGF-β信号传感器）的水平增加了2-3倍。通过I125-TGF-β-交联/Western blot分析，乙醇（0.5%）使细胞内池中II型TGF-β受体（t -β r -II）的细胞表面表达增加了~2-3倍。蔗糖密度梯度超离心和间接免疫荧光染色分析显示，乙醇（0.5%和1%）也会使细胞表面的TβR-I和TβR-II从脂筏/小泡中移位，并促进这些受体转运到非脂筏微域，在那里发生典型信号传导。这些结果表明，乙醇通过增加TGF-β受体的非脂质筏微域定位来增强典型TGF-β信号传导。由于TGF-β在ASCVD中起保护作用，但也可引起ALD，低剂量和高剂量乙醇的TGF-β增强剂活性似乎对有益和有害的影响都有影响。乙醇还会破坏其他膜蛋白（如神经递质、生长因子/细胞因子和G蛋白偶联受体）的脂筏/小泡的位置，这些膜蛋白利用脂筏/小泡作为信号平台。乙醇引起的这些膜蛋白的移位可能导致神经、心脏和其他组织的各种病理。
Regular consumption of moderate amounts of ethanol has important health benefits on atherosclerotic cardiovascular disease (ASCVD). Overindulgence can cause many diseases, particularly alcoholic liver disease (ALD). The mechanisms by which ethanol causes both beneficial and harmful effects on human health are poorly understood. Here we demonstrate that ethanol enhances TGF-β-stimulated luciferase activity with a maximum of 0.5–1% (v/v) in Mv1Lu cells stably expressing a luciferase reporter gene containing Smad2-dependent elements. In Mv1Lu cells, 0.5% ethanol increases the level of P-Smad2, a canonical TGF-β signaling sensor, by ~2-3-fold. Ethanol (0.5%) increases cell-surface expression of the type II TGF-β receptor (TβR-II) by ~2-3-fold from its intracellular pool, as determined by I125-TGF-β-cross-linking/Western blot analysis. Sucrose density gradient ultracentrifugation and indirect immunofluorescence staining analyses reveal that ethanol (0.5% and 1%) also displaces cell-surface TβR-I and TβR-II from lipid rafts/caveolae and facilitates translocation of these receptors to non-lipid raft microdomains where canonical signaling occurs. These results suggest that ethanol enhances canonical TGF-β signaling by increasing non-lipid raft microdomain localization of the TGF-β receptors. Since TGF-β plays a protective role in ASCVD but can also cause ALD, the TGF-β enhancer activity of ethanol at low and high doses appears to be responsible for both beneficial and harmful effects. Ethanol also disrupts the location of lipid raft/caveolae of other membrane proteins (e.g., neurotransmitter, growth factor/cytokine, and G protein-coupled receptors) which utilize lipid rafts/caveolae as signaling platforms. Displacement of these membrane proteins induced by ethanol may result in a variety of pathologies in nerve, heart and other tissues.
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影响因子：
2.9
作者：
ABE, M;HARPEL, JG;RIFKIN, DB
通讯作者：
RIFKIN, DB
影响因子：
5.3
作者：
Assaife-Lopes, Natalia;Sousa, Vasco C.;Sebastiao, Ana M.
通讯作者：
Sebastiao, Ana M.
影响因子：
37.8
作者：
FagotCampagna, A;Hanson, RL;Knowler, WC
通讯作者：
Knowler, WC
DOI：
10.1111/j.1530-0277.2011.01479.x
发表时间：
2011-08-01
影响因子：
3.2
作者：
Ghare, Smita;Patil, Madhuvanti;Joshi-Barve, Swati
通讯作者：
Joshi-Barve, Swati
影响因子：
3.3
作者：
Dore, JJE;Yao, DY;Leof, EB
通讯作者：
Leof, EB