Back to Search
Start Over
zP2[X.sub.7] receptor-mediated apoptosis of human cervical epithelial cells
- Source :
- The American Journal of Physiology. Nov, 2004, Vol. 287 Issue 5, pC1349, 10 p.
- Publication Year :
- 2004
-
Abstract
- P2[X.sub.7] receptor-mediated apoptosis of human cervical epithelial cells. Am J Physiol Cell Physiol 287: C1349-C1358, 2004. First published July 21, 2004; doi:10.1152/ ajpcell.00256.2004.--Normal human ectocervical epithelial (hECE) cells undergo apoptosis in culture. Baseline apoptosis could be increased by shifting cells to serum-free medium and blocked by lowering extracellular calcium. Treatment with the ATPase apyrase attenuated baseline apoptosis, suggesting that extracellular ATP and purinergic mechanisms control the apoptosis. Treatment with ATP and the P2[X.sub.7] receptor analog 2'-3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) increased apoptosis significantly, in a time-and dose-related manner. The threshold of ATP effect was 0.5 [micro]M in hECE cells and ~1 [micro]M in CaSki cancer cells. The apoptotic effect of BzATP was additive in part to that of tumor necrosis factor (TNF)-[alpha], and it could be attenuated by lowering extracellular calcium and by treatment with the caspase-9 inhibitor Leu-Glu-His-Asp-O-methylfluoromethylketone (LEHD-FMK). Treatment with BzATP activated caspase-9, and, in contrast to TNF-[alpha], it had only a mild effect on caspase-8. Both BzATP and TNF-[alpha] activated caspase-3, suggesting that BzATP activates predominantly the mitochondrial apoptotic pathway. Both hECE and CaSki cells secrete ATP into the extracellular fluid, and mean ATP activity in conditioned medium was ~0.5 [micro]M, which is in the range of values that suffice to activate the P2[X.sub.7] receptor. On the basis of these findings we propose a novel autocrineparacrine mechanism of cervical cell apoptosis that operates by P2[X.sub.7] receptor control of cytosolic calcium and utilizes the mitochondrial apoptotic pathway. cervix; epithelium; ATP; 2'-3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate
- Subjects :
- Epithelium -- Research
Apoptosis -- Research
Biological sciences
Subjects
Details
- Language :
- English
- ISSN :
- 00029513
- Volume :
- 287
- Issue :
- 5
- Database :
- Gale General OneFile
- Journal :
- The American Journal of Physiology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.125149192