Levonorgestrel Inhibits Human Endometrial Cell Proliferation through the Upregulation of Gap Junctional Intercellular Communication via the Nuclear Translocation of Ser255 Phosphorylated Cx43
Levonorgestrel Inhibits Human Endometrial Cell Proliferation through the Upregulation of Gap Junctional Intercellular Communication via the Nuclear Translocation of Ser255 Phosphorylated Cx43
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左炔诺孕酮通过 Ser255 磷酸化 Cx43 的核易位上调间隙连接细胞间通讯来抑制人子宫内膜细胞增殖
DOI：
10.1155/2015/758684
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发表时间：
2015-06
影响因子：
--
通讯作者：
Yang D
中科院分区：
文献类型：
--
作者：
Ma T;Ding M;Bian L;Chen D;Li Y;Wang L;Zhuang Y;Xie M;Yang D
对象探讨LNG是否通过改变GJIC功能和磷酸化Cx43对人子宫内膜细胞产生抗增殖作用。方法. LNG对人子宫内膜间质细胞（HESC）和腺细胞（HEGCs）增殖和凋亡的影响具有剂量和时间依赖性。测量GJIC变化和进一步的总Cx43和丝氨酸368和255磷酸化Cx43。结果5 × 10−5 mol/L LNG对HESCs和HEGCs的增殖有时间依赖性的抑制作用，并增加细胞凋亡。此外，这些细胞在5 × 10−5 mol/L处理48小时后表现出显著的GJIC增强。LNG的影响在HESC中而不是在HEGC中最明显。与这些变化相关联，LNG以时间依赖性方式诱导总Cx43的相对增加，但不诱导Ser 368磷酸化Cx43。激光扫描共聚焦显微镜观察证实了细胞质中总Cx43的表达增加，有趣的是，Ser 255磷酸化的Cx43发生了核转位。结论. LNG可能抑制HESC和HEGC的增殖并促进细胞凋亡，尽管体外间隙连接通透性增加，这是通过上调Cx43表达和丝氨酸255磷酸化的Cx43从血浆转运到核区室来实现的。
Objects. To assess whether LNG exerts antiproliferation effects on human endometrial cells through changes of GJIC function and the phosphorylated Cx43. Methods. Cell proliferation and apoptosis of human endometrial stromal cells (HESCs) and glandular cells (HEGCs) treated with LNG in a dose- and time-dependent manner. GJIC change and further total Cx43 and serine 368 and 255 phosphorylated Cx43 were measured. Results. 5 × 10−5 mol/L LNG revealed a time-dependent inhibition of cell proliferation and an increase of apoptosis in both HESCs and HEGCs. Furthermore, these cells demonstrated a significant GJIC enhancement upon treatment with 5 × 10−5 mol/L for 48 hours. The effects of LNG were most noticeable in HESCs rather than in HEGCs. Associated with these changes, LNG induced a relative increase in total Cx43 in a time-dependent manner but not Ser368 phosphorylated Cx43. Moreover, laser scanning confocal microscope confirmed the increased expression of total Cx43 in the cytoplasm and, interestingly, the nuclear translocation of Ser255 phosphorylated Cx43. Conclusions. LNG likely inhibits the proliferation and promotes apoptosis in HESCs and HEGCs though an increase in gap junction permeability in vitro, which is achieved through the upregulation of Cx43 expression and the translocation of serine 255 phosphorylated Cx43 from the plasma to the nuclear compartment.
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影响因子：
4.6
作者：
Norris, Rachael P.;Freudzon, Marina;Mehlmann, Lisa M.;Cowan, Ann E.;Simon, Alexander M.;Paul, David L.;Lampe, Paul D.;Jaffe, Laurinda A.
通讯作者：
Jaffe, Laurinda A.
影响因子：
2
作者：
M. Årnes;B. Hvingel;A. Orbo
通讯作者：
M. Årnes;B. Hvingel;A. Orbo
DOI：
10.1210/jcem.78.3.8126136
发表时间：
1994-03
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
I. Ryan;E. Schriock;Robert N. Taylor
通讯作者：
I. Ryan;E. Schriock;Robert N. Taylor
影响因子：
3.6
作者：
Schlemmer, SR;Novotny, DB;Kaufman, DG
通讯作者：
Kaufman, DG
影响因子：
4.6
作者：
S. Schlemmer;D. Kaufman
通讯作者：
S. Schlemmer;D. Kaufman