DMSO Enhances TGF-β Activity by Recruiting the Type II TGF-β Receptor From Intracellular Vesicles to the Plasma Membrane.
DMSO Enhances TGF-β Activity by Recruiting the Type II TGF-β Receptor From Intracellular Vesicles to the Plasma Membrane.
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DOI：
10.1002/jcb.25448
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发表时间：
2016-07
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;Hou WH;Huang JS
二甲基亚砜（DMSO）用于治疗许多疾病/症状。DMSO药理作用的分子基础尚不清楚。我们假设DMSO通过增强TGF-β活性来发挥其中的一些作用。本研究表明，在表达smad依赖性荧光素酶报告基因的Mv1Lu和NMuMG细胞中，DMSO可将TGF-β活性提高约3 - 4倍。在Mv1Lu细胞中，DMSO增强TGF-β刺激的P-Smad2和PAI-1的表达。通过125i标记的TGF-β交联/Western blot分析，它使TGF-β受体（TβR-I和/或TβR-II）的细胞表面表达增加了~3 - 4倍，而不改变其细胞水平，表明这些细胞中存在大的细胞内池。蔗糖密度梯度超离心/Western blot分析显示，DMSO诱导TβR-II（而不是TβR-I）从胞内池募集到质膜微域。它诱导更多的t - β r - ii募集到非脂筏微结构域，而不是脂筏/小泡。用DMSO处理瞬时转染t - β r - ii - ha质粒的Mv1Lu细胞，用抗ha抗体间接免疫荧光染色分析。在这些细胞中，t - β r - ii - ha以囊泡样网络的形式存在于细胞质和质膜中。DMSO导致细胞质中含有TβR-II-HA的囊泡耗损，并导致TβR-II-HA和cveolin-1在质膜上共定位。这些结果表明，DMSO（一种融合物质）可能通过诱导细胞质囊泡（含有TβR-II）与质膜融合来增强TGF-β活性，导致TβR-II增加定位到典型信号发生的非脂质筏微结构域。DMSO的促聚变活性可能在其涉及具有大细胞质池的膜蛋白的药理作用中起关键作用。
Dimethyl sulfoxide (DMSO) is used to treat many diseases/symptoms. The molecular basis of the pharmacological actions of DMSO has been unclear. We hypothesized that DMSO exerts some of these actions by enhancing TGF-β activity. Here we show that DMSO enhances TGF-β activity by ~3–4-fold in Mv1Lu and NMuMG cells expressing Smad-dependent luciferase reporters. In Mv1Lu cells, DMSO enhances TGF-β-stimulated expression of P-Smad2 and PAI-1. It increases cell-surface expression of TGF-β receptors (TβR-I and/or TβR-II) by ~3–4-fold without altering their cellular levels as determined by 125I-labeled TGF-β-cross-linking/Western blot analysis, suggesting the presence of large intracellular pools in these cells. Sucrose density gradient ultracentrifugation/Western blot analysis reveals that DMSO induces recruitment of TβR-II (but not TβR-I) from its intracellular pool to plasma-membrane microdomains. It induces more recruitment of TβR-II to non-lipid raft microdomains than to lipid rafts/caveolae. Mv1Lu cells transiently transfected with TβR-II-HA plasmid were treated with DMSO and analyzed by indirect immunofluoresence staining using anti-HA antibody. In these cells, TβR-II-HA is present as a vesicle-like network in the cytoplasm as well as in the plasma membrane. DMSO causes depletion of TβR-II-HA-containing vesicles from the cytoplasm and co-localization of TβR-II-HA and cveolin-1 at the plasma membrane. These results suggest that DMSO, a fusogenic substance, enhances TGF-β activity presumably by inducing fusion of cytoplasmic vesicles (containing TβR-II) and the plasma membrane, resulting in increased localization of TβR-II to non-lipid raft microdomains where canonical signaling occurs. Fusogenic activity of DMSO may play a pivotal role in its pharmacological actions involving membrane proteins with large cytoplasmic pools.
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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：
3.3
作者：
Dore, JJE;Yao, DY;Leof, EB
通讯作者：
Leof, EB
DOI：
10.1073/pnas.75.5.2458
发表时间：
1978-01-01
影响因子：
11.1
作者：
COLLINS, SJ;RUSCETTI, FW;GALLO, RC
通讯作者：
GALLO, RC
影响因子：
2.1
作者：
FOWLER, JE
通讯作者：
FOWLER, JE
DOI：
10.1006/bbrc.1994.2846
发表时间：
1994-12-30
影响因子：
3.1
作者：
BRUNGS, M;RADMARK, O;STEINHILBER, D
通讯作者：
STEINHILBER, D