cytochrome-c-t and Leiomyoma

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.. 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.. 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.. 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.

Topics: Adult; Apoptosis; Calcium; Calcium Channel Blockers; Cell Hypoxia; Cells, Cultured; Cytochromes c; Female; Gene Expression; Humans; Inositol 1,4,5-Trisphosphate Receptors; Ischemia; Laparoscopy; Leiomyoma; Middle Aged; Myometrium; RNA, Messenger; Ryanodine Receptor Calcium Release Channel; Uterine Artery; Uterine Neoplasms; Uterus

Myoma therapy by uterine artery occlusion using laparoscopic ligation (UAOL) has been performed for many years and has proven effective, but limited information is available on its therapeutic mechanism. To examine this issue, we conducted this study to investigate the morphological change and apoptosis occurring in myomal and adjacent myometrial tissues shortly after UAOL.. In total, 16 myomas and adjacent myometrium were obtained from 7 cases before and at various points after artery ligation. The tissues were stained using hematoxylin and eosin for morphological observation. To investigate the existence of apoptosis, in situ immunostaining of Caspase 3 and TUNEL assay were performed. Cytochrome C released from mitochondria was also detected by immunohistochemistry.. Microscopic observation found that after UAOL, both myometrial and myomal tissues were edematous and apoptotic cells were widespread in both tissues. TUNEL assays showed that before UAOL, numbers of apoptotic cells in myomal and myometrial tissues had no significant differences (P=0.866). After ischemia of (36.69+/-18.53) min, apoptosis was significantly more elevated in myoma than in myometrium ((6.43+/-4.38)/10 HPF vs. (2.74+/-1.95)/10 HPF, P=0.003). Caspase 3 stain shared similar features with the TUNEL assay. In both groups cytochrome C was released from mitochondria after UAOL, and more was detected in the myoma.. UAOL is an alternative method to treat symptomatic uterine myomas. Apoptosis via mitochondrial pathways may lead to reduction of the volume of myoma and myometrium and eventual relief of symptoms.

Topics: Adult; Apoptosis; Caspase 3; Cytochromes c; Female; Humans; Laparoscopy; Leiomyoma; Ligation; Middle Aged; Mitochondria; Myometrium; Regression Analysis; Retrospective Studies; Uterine Artery Embolization; Uterine Neoplasms; Uterus