title: Calcium concentration response to uterine ischemia: a comparison of uterine fibroid cells and adjacent normal myometrial cells.
abstract: OBJECTIVE
  Uterine artery occlusion by laparoscopy (UAOL) has been used for the treatment of uterine fibroids and beneficial effects to patients have been shown in clinical studies since 2000. Fibroid cells are more susceptible to apoptosis than myometrial cells under hypoxic conditions, but the molecular mechanisms underlying this effect remain unclear. The aim of this study was to investigate the role of intracellular calcium (Ca(2+)) release mediated by Ca(2+) channel inositol 1,4,5 trisphosphate receptor1 (IP3R1)/ryanodine receptor1 (RYR1) in the apoptosis of uterine fibroid cells under hypoxia.
  
  
  METHODS
  We compared the expressions of IP3R1 and RYR1 in fibroid and surrounding myometrial tissue from 20 patients before UAOL. After 6h treatment under hypoxia (1% O2) with or without Ca(2+) channel blockers (heparin or/and ruthenium red), the intracellular Ca(2+) concentration, cytochrome c (Cytc) protein and cell apoptosis were determined.
  
  
  RESULTS
  IP3R1 and RYR1 mRNA and protein levels were significantly higher in fibroid than in myometrial tissues. Under hypoxic conditions, Ca(2+) concentration in fibroid cells was significantly higher than in myometrial cells (Ca(2+): 82.69±16.92nmol/L vs 46.14±9.11nmol/L, P<0.05), and Cytc increased similarly in fibroid cells. These increases in Ca(2+) concentration, Cytc and cell apoptosis were significantly reversed by calcium blocker in fibroid cells.
  
  
  CONCLUSIONS
  This study demonstrated that intracellular calcium release mediated by IP3R1/RYR1 could induce apoptosis in uterine fibroid cells under hypoxic conditions, and was responsible for the susceptibility to apoptosis of fibroid cells under UAOL.
authors.affiliation: Department of Obstetrics and Gynecology, Yang-Pu Center Hospital, Shanghai, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Yang-Pu Center Hospital, Shanghai, China. Electronic address: mdcheng18@263.net.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, Yang-Pu Center Hospital, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Dai
mesh_terms: D000328:Adult; D017209:Apoptosis; D002118:Calcium / Q000032:analysis* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D045304:Cytochromes c / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000032:analysis / Q000235:genetics / Q000502:physiology; D007511:Ischemia; D010535:Laparoscopy; D007889:Leiomyoma / Q000737:chemistry* / Q000601:surgery; D008875:Middle Aged; D009215:Myometrium / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis / Q000235:genetics / Q000502:physiology; D055988:Uterine Artery / Q000601:surgery; D014594:Uterine Neoplasms / Q000737:chemistry* / Q000601:surgery; D014599:Uterus / Q000098:blood supply*
chemical_list: D002121:Calcium Channel Blockers; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D045304:Cytochromes c; D002118:Calcium
keywords: Apoptosis; Calcium release; Fibroids; Uterine artery occlusion