Gap Junctional Communication and Connexin43 Expression in Relation to Apoptotic Cell Death and Survival of Granulosa Cells

Abstract

S U M M A R YOvarian follicular atresia in all vertebrates is mediated via apoptosis that is initiated in the granulosa cell layer. Here we investigated the relation between connexin expression, cell coupling, and apoptosis in avian granulosa cells. Results from qualitative and quantitative immunocytochemical analysis and Western blotting of connexin43 (Cx43) and electron microscopic observations of gap junctions were compared with functional data on gap junctional coupling obtained by fluorescence recovery after photobleaching in four experimental groups: a control group of freshly isolated granulosa cells, 24-hr serumfree cultures as the apoptosis-inducing condition, and two other groups in which apoptosis was inhibited by either hormone substitution or exposure to elevated extracellular calcium. Our work shows that apoptosis induction in granulosa cells is accompanied by an increased level of cell coupling and that decreasing cell coupling with the gap junction blocker ␣ -glycyrrhetinic acid dose-dependently inhibits apoptosis. The level of Cx43 expression was inversely related to the apoptotic index, suggesting that Cx43 expression plays a role in granulosa cell survival. Our study supports the hypothesis that gap junctional coupling plays a role in propagating a cell death message and suggests a role for Cx43 expression per se in granulosa cell survival.

Primordial germ cell deficiency in the connexin 43 knockout mouse arises from apoptosis associated with abnormal p53 activation

“…Treatment of wellcoupled GFSHR-17 granulosa cells with gap junction uncouplers has been reported to promote apoptosis (Ngezahayo et al, 2005). However, in primary granulosa cells, the induction of apoptosis was actually associated with increased cell coupling, and upon gap junction blockade, apoptosis was inhibited (Krysko et al, 2004). We note that a specific role for Cx43␣1 in apoptosis has been suggested in a number of other studies (Albright et al, 2001;Furlan et al, 2001;Nakase et al, 2004;Yasui et al, 2000).…”

Role of Connexin 43 in Helicobacter pylori VacA-Induced Cell Death

“…Direct intercellular communication by gap junctions is mediated primarily by passive diffusion of small hydrophilic molecules, such as glucose, glutamate, glutathione, cAMP, ATP, inositol triphosphate (IP 3 ), calcium, potassium, and sodium (48,54,74). Gap junction proteins (and Cx43 in particular) can regulate cell death and survival, cell growth, and cell differentiation through several mechanisms, which are either dependent or independent of channel activity (79)(80)(81)(82)(83). Cx43 has been localized not only to gap junctions but also to intracellular sites, including mitochondria (48,76,79,80,84).…”

Inhibition of gap junction intercellular communication is involved in silica nanoparticles-induced H9c2 cardiomyocytes apoptosis via the mitochondrial pathway

“…Several studies have shown that changes in GJIC can influence cell survival or apoptosis. [28][29][30] In rat ventricular myocytes, reduced Cx43 expression resulted in increased apoptosis. 31 Similar effects were found in mammary epithelial cells with lower connexin 26 expression.…”