Abstract
Recent results have shown that the level of gap junction coupling could modulate the induction of apoptotic reactions. We previously observed that 1H-[1,2, 4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ), a block- er of guanylyl cyclase, inhibited gap junction coupling and thereby promoted activation of characteristic apoptotic reactions such as chromatin condensation, DNA strand breaking, and formation of blebs in GFSHR-17 granulosa cells, the in vitro model for granulosa cells of the maturing ovular follicle. In the present report, we focus on the effects of ODQ with respect to the cell cycle in GFSHR-17 granulosa cells. In synchronised GFSHR-17 granulosa cells, the double whole-cell patch-clamp technique revealed that gap junction conductance in mitotic cells was reduced in comparison to cells in interphase. This reduction of gap junction conductance correlated with a reduction of non-phosphorylated Cx43 in mitotic cells. We compared the stimulation of apoptotic reactions by ODQ between cells in mitosis and in interphase. We observed that the induction of both chromatin condensation and DNA strand breaking by ODQ was increased in mitotic cells, as compared to cells in interphase. The effects of ODQ were not observed in He-La cells that do not express connexins. The results in- dicate that reduction of gap junction coupling in mitotic GFSHR-17 granulosa cells depends on phosphor- rylation of Cx43 and raises the sensitivity to stimulation of apoptosis. We propose that gap junction coupling is involved in regulation of apoptosis of granulosa cells in maturing ovular follicle.
Highlights
Gap junctions are adhesion structures containing cellto-cell channels that enable neighbouring cells to exchange small molecules (≤ 1 kDa) like Ca2+, cAMP, IP3, and to synchronise electrical as well as physiological activities [1,2]
The results indicate that reduction of gap junction coupling in mitotic GFSHR-17 granulosa cells depends on phosphorrylation of Cx43 and raises the sensitivity to stimulation of apoptosis
We propose that gap junction coupling is involved in regulation of apoptosis of granulosa cells in maturing ovular follicle
Summary
Gap junctions are adhesion structures containing cellto-cell channels that enable neighbouring cells to exchange small molecules (≤ 1 kDa) like Ca2+, cAMP, IP3, and to synchronise electrical as well as physiological activities [1,2]. Gap junction channels are composed of connexins (Cx), which are the products of 19 and 20 genes in mouse and human, respectively. Gap junction assembly involves oligomerisation of six connexins in order to form a connexon that is inserted into the cellular membrane. Two connexons of adjacent cells associate and form a cell-to-cell channel. Since gap junction channels allow a direct intercellular exchange of metabolites and second messengers, specific roles in diseases and regulation of cellular activities including proliferation, transformation, differentiation and apoptosis have been hypothesised [2,4]
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