Details
| Original language | English |
|---|---|
| Pages (from-to) | 137-44 |
| Number of pages | 8 |
| Journal | The journal of membrane biology |
| Volume | 204 |
| Issue number | 3 |
| Publication status | Published - Apr 2005 |
Abstract
Recently, we found that intracellular washout of cGMP induces gap junction uncoupling and proposed a link between gap junction uncoupling and stimulation of apoptotic reactions in GFSHR-17 granulosa cells. In the present report we show that an inhibitor of guanylyl cyclase, ODQ, reduces gap junction coupling and promotes apoptotic reactions such as chromatin condensation and DNA strand breaks. To analyze whether gap junction uncoupling and induction of apoptotic reactions are related, the cells were treated with heptanol and 18 beta-GA, two known gap junction uncouplers. Gap junction coupling of GFSHR-17 cells could be restored if the incubation time with the gap junction uncouplers was less than 10 min. A prolonged incubation time irreversibly suppressed gap junction coupling and caused chromatin condensation as well as DNA degradation. The promotion of apoptotic reactions by heptanol or 18 beta-GA was not observed in cells with low gap junction coupling like HeLa cells, indicating that the observed genotoxic reactions are not caused by unspecific effects of gap junction uncouplers. Additionally, it was observed that heptanol or 18 beta-GA did not induce a sustained rise of [Ca(2+)](i). The effects of gap junction uncouplers could not be suppressed by the presence of 8-Br-cGMP. It is discussed that irreversible gap junction uncoupling can be mediated by cGMP-dependent as well as cGMP-independent pathways and in turn could lead to stimulation of apoptotic reactions in granulosa cells.
Keywords
- Apoptosis/drug effects, Cell Line, DNA/drug effects, DNA Damage, Dose-Response Relationship, Drug, Female, Gap Junctions/drug effects, Granulosa Cells/cytology, HeLa Cells, Humans, Oxadiazoles/administration & dosage, Quinoxalines/administration & dosage
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In: The journal of membrane biology, Vol. 204, No. 3, 04.2005, p. 137-44.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Gap junction coupling and apoptosis in GFSHR-17 granulosa cells
AU - Ngezahayo, A
AU - Altmann, Bianca
AU - Steffens, M
AU - Kolb, H-A
PY - 2005/4
Y1 - 2005/4
N2 - Recently, we found that intracellular washout of cGMP induces gap junction uncoupling and proposed a link between gap junction uncoupling and stimulation of apoptotic reactions in GFSHR-17 granulosa cells. In the present report we show that an inhibitor of guanylyl cyclase, ODQ, reduces gap junction coupling and promotes apoptotic reactions such as chromatin condensation and DNA strand breaks. To analyze whether gap junction uncoupling and induction of apoptotic reactions are related, the cells were treated with heptanol and 18 beta-GA, two known gap junction uncouplers. Gap junction coupling of GFSHR-17 cells could be restored if the incubation time with the gap junction uncouplers was less than 10 min. A prolonged incubation time irreversibly suppressed gap junction coupling and caused chromatin condensation as well as DNA degradation. The promotion of apoptotic reactions by heptanol or 18 beta-GA was not observed in cells with low gap junction coupling like HeLa cells, indicating that the observed genotoxic reactions are not caused by unspecific effects of gap junction uncouplers. Additionally, it was observed that heptanol or 18 beta-GA did not induce a sustained rise of [Ca(2+)](i). The effects of gap junction uncouplers could not be suppressed by the presence of 8-Br-cGMP. It is discussed that irreversible gap junction uncoupling can be mediated by cGMP-dependent as well as cGMP-independent pathways and in turn could lead to stimulation of apoptotic reactions in granulosa cells.
AB - Recently, we found that intracellular washout of cGMP induces gap junction uncoupling and proposed a link between gap junction uncoupling and stimulation of apoptotic reactions in GFSHR-17 granulosa cells. In the present report we show that an inhibitor of guanylyl cyclase, ODQ, reduces gap junction coupling and promotes apoptotic reactions such as chromatin condensation and DNA strand breaks. To analyze whether gap junction uncoupling and induction of apoptotic reactions are related, the cells were treated with heptanol and 18 beta-GA, two known gap junction uncouplers. Gap junction coupling of GFSHR-17 cells could be restored if the incubation time with the gap junction uncouplers was less than 10 min. A prolonged incubation time irreversibly suppressed gap junction coupling and caused chromatin condensation as well as DNA degradation. The promotion of apoptotic reactions by heptanol or 18 beta-GA was not observed in cells with low gap junction coupling like HeLa cells, indicating that the observed genotoxic reactions are not caused by unspecific effects of gap junction uncouplers. Additionally, it was observed that heptanol or 18 beta-GA did not induce a sustained rise of [Ca(2+)](i). The effects of gap junction uncouplers could not be suppressed by the presence of 8-Br-cGMP. It is discussed that irreversible gap junction uncoupling can be mediated by cGMP-dependent as well as cGMP-independent pathways and in turn could lead to stimulation of apoptotic reactions in granulosa cells.
KW - Apoptosis/drug effects
KW - Cell Line
KW - DNA/drug effects
KW - DNA Damage
KW - Dose-Response Relationship, Drug
KW - Female
KW - Gap Junctions/drug effects
KW - Granulosa Cells/cytology
KW - HeLa Cells
KW - Humans
KW - Oxadiazoles/administration & dosage
KW - Quinoxalines/administration & dosage
U2 - 10.1007/s00232-005-0756-5
DO - 10.1007/s00232-005-0756-5
M3 - Article
C2 - 16245036
VL - 204
SP - 137
EP - 144
JO - The journal of membrane biology
JF - The journal of membrane biology
SN - 0022-2631
IS - 3
ER -