Gap junction coupling and apoptosis in GFSHR-17 granulosa cells
A Ngezahayo1, B Altmann, M Steffens
1Institute of Biophysics, University Hannover, Herrenhäuserstr. 2, D-30419 Hannover, Germany. ngezahayo@biophysik.uni-hannover.de
The Journal of Membrane Biology
|October 26, 2005
Summary
Intracellular washout of cyclic guanosine monophosphate (cGMP) causes gap junction uncoupling and apoptosis in granulosa cells. This study confirms that gap junction uncoupling, via various agents, triggers cell death pathways.
Area of Science:
- Cell Biology
- Molecular Biology
- Reproductive Biology
Background:
- Intracellular cyclic guanosine monophosphate (cGMP) washout was previously linked to gap junction uncoupling and apoptosis in GFSHR-17 granulosa cells.
- Gap junction communication is crucial for cellular homeostasis and function, particularly in granulosa cells of the reproductive system.
Purpose of the Study:
- To investigate the relationship between gap junction uncoupling and the induction of apoptotic reactions in GFSHR-17 granulosa cells.
- To determine if cGMP signaling pathways are involved in mediating the effects of gap junction uncoupling on apoptosis.
Main Methods:
- Treatment of GFSHR-17 granulosa cells with guanylyl cyclase inhibitor ODQ.
- Application of gap junction uncouplers heptanol and 18 beta-glycyrrhetinic acid (18 beta-GA).
- Assessment of gap junction coupling, chromatin condensation, DNA strand breaks, and intracellular calcium levels ([Ca(2+)](i)).
Main Results:
- ODQ treatment reduced gap junction coupling and promoted apoptosis, evidenced by chromatin condensation and DNA strand breaks.
- Prolonged incubation with heptanol or 18 beta-GA irreversibly suppressed gap junction coupling and induced apoptosis.
- Apoptotic reactions were not observed in HeLa cells with low gap junction coupling, suggesting specificity.
- Heptanol and 18 beta-GA did not cause sustained increases in [Ca(2+)](i), and their effects were not reversed by 8-Br-cGMP.
Conclusions:
- Irreversible gap junction uncoupling can stimulate apoptotic reactions in granulosa cells.
- Both cGMP-dependent and cGMP-independent pathways may mediate irreversible gap junction uncoupling.
- Gap junction uncoupling represents a potential trigger for apoptosis in granulosa cells, independent of significant calcium influx.
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