title: Levonorgestrel Inhibits Human Endometrial Cell Proliferation through the Upregulation of Gap Junctional Intercellular Communication via the Nuclear Translocation of Ser255 Phosphorylated Cx43.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Xiaomiao
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Shenzhen Maternity and Child Care Centers, Southern Medical University, Shenzhen, Guangdong 518000, China.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Ding
authors.affiliation: Pathology Department, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Bian
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Yangzhi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Liangan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou 215325, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China.
authors.forename: Dongzi
authors.initials: D
authors.lastname: Yang
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D018031:Connexin 43 / Q000097:blood / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D016912:Levonorgestrel / Q000494:pharmacology*; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; D010768:Phosphoserine; D016912:Levonorgestrel