Calcium concentration response to uterine ischemia: a comparison of uterine fibroid cells and adjacent normal myometrial cells

ObjectiveUterine 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 (Ca2+) release mediated by Ca2+ channel inositol 1,4,5 trisphosphate receptor1 (IP3R1)/ryanodine receptor1 (RYR1) in the apoptosis of uterine fibroid cells under hypoxia.Study designWe compared the expressions of IP3R1 and RYR1 in fibroid and surrounding myometrial tissue from 20 patients before UAOL. After 6 h treatment under hypoxia (1% O2) with or without Ca2+ channel blockers (heparin or/and ruthenium red), the intracellular Ca2+ concentration, cytochrome c (Cytc) protein and cell apoptosis were determined.ResultsIP3R1 and RYR1 mRNA and protein levels were significantly higher in fibroid than in myometrial tissues. Under hypoxic conditions, Ca2+ concentration in fibroid cells was significantly higher than in myometrial cells (Ca2+: 82.69 ± 16.92 nmol/L vs 46.14 ± 9.11 nmol/L, P < 0.05), and Cytc increased similarly in fibroid cells. These increases in Ca2+ concentration, Cytc and cell apoptosis were significantly reversed by calcium blocker in fibroid cells.ConclusionThis 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.