Gap junctions in the ovary: Expression, localization and function

Gershon, Eran; Plaks, Vicki; Dekel, Nava

doi:10.1016/j.mce.2007.11.001

Cited by 122 publications

(92 citation statements)

References 112 publications

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“…In larger lung tumors, Cx32 and Cx40 are down-regulated, but Cx37, Cx43, and Cx45 are expressed (Isakson et al, 2001a(Isakson et al, ,b, 2003Udaka et al, 2006). In other cases, such as ovarian adenocarcinomas and cervical cancer, GJIC is dramatically reduced (Hanna et al, 1999;Umhauer et al, 2000;Aasen et al, 2005;Gershon et al, 2008). In this situation, because GJIC is already essentially absent, the effect of platinating reagents described in the present study would not occur, but in the former cases, the effect on the efficacy of the drugs due to effects on GJIC could occur.…”

Section: Downloaded Frommentioning

confidence: 56%

Cisplatin and Oxaliplatin Inhibit Gap Junctional Communication by Direct Action and by Reduction of Connexin Expression, Thereby Counteracting Cytotoxic Efficacy

Wang

You²,

Yuan³

et al. 2010

J Pharmacol Exp Ther

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Cisplatin [cis-diamminedichloroplatinum(II)]/oxaliplatin [1,2-diamminocyclohexane(trans-1)oxolatoplatinum(II)] toxicity is enhanced by functional gap junctions between treated cells, implying that inhibition of gap junctions may decrease cytotoxic activity of these platinum-based agents. This study investigates the effect of gap junction modulation by cisplatin/oxaliplatin on cytotoxicity in a transformed cell line. The effects were explored using junctional channels expressed in transfected HeLa cells and purified hemichannels. Junctional channels showed a rapid, dose-dependent decrease in dye coupling with exposure to cisplatin/oxaliplatin. With longer exposure, both compounds also decreased connexin expression. Both compounds inhibit the activity of purified connexin hemichannels, over the same concentration range that they inhibit junctional dye permeability, demonstrating that inhibition occurs by direct interaction of the drugs with connexin protein. Cisplatin/oxaliplatin reduced the clonogenic survival of HeLa cells at low density and high density in a dose-dependent manner, but to a greater degree at high density, consistent with a positive effect of gap junctional intercellular communication (GJIC) on cytotoxicity. Reduction of GJIC by genetic or pharmacological means decreased cisplatin/oxaliplatin toxicity. At low cisplatin/oxaliplatin concentrations, where effects on connexin channels are minimal, the toxicity increased with increased cell density. However, higher concentrations strongly inhibited GJIC, and this counteracted the enhancing effect of greater cell density on toxicity. The present results indicate that inhibition of GJIC by cisplatin/ oxaliplatin decreases their cytotoxicity. Direct inhibition of GJIC and reduction of connexin expression by cisplatin/oxaliplatin may thereby compromise the effectiveness of these compounds and be a factor in the development of resistance to this class of chemotherapeutic agents.

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Section: Downloaded Frommentioning

confidence: 56%

Cisplatin and Oxaliplatin Inhibit Gap Junctional Communication by Direct Action and by Reduction of Connexin Expression, Thereby Counteracting Cytotoxic Efficacy

Wang

You²,

Yuan³

et al. 2010

J Pharmacol Exp Ther

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“…Gap junction proteins play a significant role in the regulation of steroidogenesis, cell proliferation, and also cell survival. Changes in cell proliferation, apoptosis, and GJA1 production are associated with follicular growth and development or atresia (Jablonka-Shariff et al 1994, Grazul-Bilska et al 1997, Ackert et al 2001, Kidder & Mhawi 2002, Gershon et al 2008.…”

Section: Introductionmentioning

confidence: 99%

Markers of ovarian antral follicular development in sheep: comparison of follicles destined to ovulate from the final or penultimate follicular wave of the estrous cycle

Seekallu¹,

Toosi²,

Grazul-Bilska³

et al. 2010

Reproduction

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Treatment of non-prolific western white-faced ewes with prostaglandin F 2a (PGF 2a ) and medroxyprogesterone acetate (MAP) increases the ovulation rate as a result of ovulations from the penultimate wave in addition to the final wave of the cycle. The objective of the current study was to evaluate the expression of markers of vascularization/angiogenesis, a marker of intercellular communication, and cellular proliferation and apoptosis in follicles from the penultimate and final waves. On day 8 of the estrous cycle, 15 ewes were administered a single injection of PGF 2a and an intravaginal MAP sponge, which remained in place for 6 days. Two days after sponge removal, ovaries which contained follicles from the penultimate and final waves were collected and processed for immunohistochemistry followed by image analysis, and for quantitative real-time RT-PCR. Expression of factor VIII (marker of vascularization), proliferating cell nuclear antigen, and GJA1 (Cx43; marker of gap junctional communication) was greater (P!0.05) in follicles from the final wave compared with follicles from the penultimate wave. For theca cells, mRNA expression for vascular endothelial growth factor (VEGF) was greater (P!0.05) and tended to be greater (P%0.1 and R0.05) for GJA1 and endothelial nitric oxide synthase in follicles from the final wave compared with follicles from the penultimate wave. For granulosa cells, the mRNA expression for GJA1 was greater (P!0.05) and tended to be greater (P%0.1 and R0.05) for VEGF in follicles from the final wave compared with follicles from the penultimate wave.In conclusion, extension of the lifespan of follicles in the penultimate wave reduces follicular viability in the ewe.

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“…This suggested that gap junctions may be involved in the regulation of steroidogenesis in the corpus luteum. Gershon et al [89] reported that the gap junctions that allow the direct communication between cytoplasmic compartments of neighboring cells are present in a variety of tissues and organs, allowing thus the rapid exchange of ions and metabolites. Besides in the bovine, follicles express Cx43, which is localized to granulosa cells from the primary follicle and increases upon antrum formation being necessary for follicle development and oocyte growth.…”

Section: The Cx43 Genementioning

confidence: 99%

Studies on Gene Expression and Developmental Competence of Bovine Embryos Produced Under Different Conditions of Heat Stress

Mahdy¹,

Pavani²,

Baron³

et al. 2017

Trends and Advances in Veterinary Genetics

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Gene expression is required in all steps of embryonic development and therefore heat stress is known to reduce developmental competence after direct exposure of oocytes and embryos to different conditions of heat shock, by decreasing protein synthesis. Moreover, as in somatic cells, the heat stress befuddles the integration of RNA and posttranscriptional modification of RNA, the assumption was that during meiotic maturation heat shock may mutate RNA within oocytes, with the possibility of altering the surrounding cumulus cells, causing, thus, reductions in development. Heat shock proteins (HSP) are among the first proteins produced during embryonic development and are crucial to cell function. The HSP70 (HSPA14 gene) is an important part of the cell's machinery for folding, unfolding, transport, localization of proteins and differentiation, regulation of the embryonic cell cycle and helping to protect cells from stress. Therefore, HSPA14 is an apoptotic gene induced by heat shock is associated with embryonic loss, playing an important role of control mechanism of processes involved in growth, cellular differentiation, and embryonic development. In addition the connexin proteins (e.g. Cx43), related to gap junctions, are expressed in numerous tissues including gonads, act as a mediator of heat stress effect on cells. In the present review, the effect of heat stress on bovine embryonic development in a physiologic and genetic point of view is fully discussed.

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Gap junctions in the ovary: Expression, localization and function

Cited by 122 publications

References 112 publications

Cisplatin and Oxaliplatin Inhibit Gap Junctional Communication by Direct Action and by Reduction of Connexin Expression, Thereby Counteracting Cytotoxic Efficacy

Cisplatin and Oxaliplatin Inhibit Gap Junctional Communication by Direct Action and by Reduction of Connexin Expression, Thereby Counteracting Cytotoxic Efficacy

Markers of ovarian antral follicular development in sheep: comparison of follicles destined to ovulate from the final or penultimate follicular wave of the estrous cycle

Studies on Gene Expression and Developmental Competence of Bovine Embryos Produced Under Different Conditions of Heat Stress

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