Transcription of the gene for the gap junctional protein connexin43 and expression of functional cell-to-cell channels are regulated by cAMP.

Mehta, Parmender P.; Yamamoto, Masao; Rose, Birgit

doi:10.1091/mbc.3.8.839

Cited by 93 publications

(65 citation statements)

References 39 publications

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“…CAMP elevating agents, like forskolin, have been described to function as gap junction up-regulators, 30 and indeed, we observed an increase in calcein transfer/ FACS in the gap junction-competent cell lines we tested. Surprisingly however, forskolin did not increase the BSE but rather enhanced tumor proliferation (Table 4), because it inhibited GCV toxicity in the hTK + cells.…”

Section: Discussionsupporting

confidence: 72%

The bystander effect in the HSVtk/ganciclovir system and its relationship to gap junctional communication

et al. 1998

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The bystander effect (BSE) is an interesting and important communication. We confirmed that mixtures of tumor cells property of the herpes thymidine kinase/ganciclovir resistant to the BSE did not show dye transfer from cell to (hTK/GCV) system of gene therapy for cancer. With the cell while bystander-sensitive tumor cells did. Dieldrin, a BSE, not only are the hTK expressing cells killed upon gandrug known to decrease GJ communication, diminished ciclovir (GCV) exposure but also neighboring wild-type dye transfer and also inhibited the BSE. Forskolin, an uptumor cells. On testing a large number of tumor cell lines regulator of cAMP did increase GJ, but directly inhibited in vitro, a wide range of sensitivity to bystander killing was hTK and therefore its effect on BSE could not be deterfound. Since transfer of toxic GCV metabolites from hTKmined. We conclude that these observations further supmodified to wild-type tumor cells via gap junctions (GJ) port the concept that functional GJ play an important role seemed to be a likely mechanism of the BSE, we tested in the BSE and further suggest that pharmacological GJ function in these various tumors with a dye transfer manipulation of GJ may influence the outcome of cancer technique and pharmacological agents known to affect GJ therapy with hTK/GCV.

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Section: Discussionsupporting

confidence: 72%

The bystander effect in the HSVtk/ganciclovir system and its relationship to gap junctional communication

et al. 1998

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“…The ability of cAMP to upregulate gap junction coupling has been demonstrated in numerous cell types including ovarian cells (Grazul-Bilska 1996, Luciano et al 2004, Thomas et al 2004. Prolonged coupling of cells in the presence of cAMP has been shown to increase the rate of synthesis of connexin mRNA or to increase stability of the transcript, thereby generating a higher rate of synthesis of gap junction protein available for assembly into new channels (Mehta et al 1992). cAMP is also postulated to induce gap junctional permeability by reapportioning Cx43 from non-junctional sites to junctional plaques at cell-cell interfaces and increase gap junction formation and membrane permeability (Azarnia et al 1981, Atkinson et al 1995.…”

Section: Discussionmentioning

confidence: 99%

Expression of connexin 43 and gap junctional intercellular communication in the cumulus–oocyte complex in sheep

Pant¹,

Reynolds²,

Luther³

et al. 2005

Reproduction

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To evaluate the effects of FSH, LH and/or cAMP on expression of connexin 43 (Cx43) in the ovine cumulus-oocyte complex (COC) and gap junctional intercellular communication (GJIC) of cumulus cells, two experiments were carried out. In experiment 1, Cx43 was immunodetected in the COC, before or after maturation, obtained from non-treated or FSH-treated ewes. The expression of Cx43 in the COC was greater (P < 0.01) on day 16 than on day 15 of the estrous cycle. In vivo FSH treatment decreased (P < 0.02) Cx43 expression on day 16 but not on day 15 of the estrous cycle. In experiment 2, intact COCs or isolated cumulus cells obtained from small and large follicles from FSH-treated ewes were cultured with or without FSH, LH or cAMP agonist and evaluated for GJIC by laser cytometry. For large follicles, the basal rate of GJIC was greater (P < 0.01) for cumulus cells in intact COCs than for isolated cumulus cells. FSH increased (P < 0.04) GJIC in cumulus cells in intact COCs and tended to increase (P < 0.1) GJIC in isolated cumulus cells from small follicles but decreased (P < 0.01) GJIC in cumulus cells in intact COCs from large follicles. LH also increased (P < 0.01) GJIC in isolated cumulus cells from small follicles but decreased GJIC in intact COCs (P < 0.01) and isolated cumulus cells (P < 0.02) from large follicles. cAMP increased (P < 0.01) the GJIC in both intact COCs and cumulus cells from small and large follicles. These results indicate that day of estrous cycle, stage of maturation and duration of FSH treatment affect expression of Cx43 in ovine COCs. In intact COCs, GJIC in cumulus cells was enhanced, probably due to the presence of the oocyte. In addition, the effects of FSH and LH, but not cAMP, on GJIC of cumulus cells depended on the stage of follicular development and on the presence of the oocyte.

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“…Mehta et al (1992) and Schiller et al (1992) reported that forskolin, an activator of adenylate cyclase, increased Cx43 mRNA 6-fold in a hepatoma cell line, with the increase preceding any detectable increase in dye coupling. Atkinson et al (1995) investigated the exposure of a mouse mammary tumor cell line, MMT22, to 8-bromo-cAMP.…”

Section: Discussionmentioning

confidence: 99%

Expression and regulation of connexin43 in rat Leydig cells

You

Li²,

Lin

2000

Journal of Endocrinology

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Gap junctions are intercellular protein channels which provide a pathway for the exchange of ions and small molecules. This exchange of materials allows metabolic coupling of cells. Gap junction channels are made up of connexins, integral membrane proteins encoded by a multigene family. Rat testes contain mRNAs for at least five different connexins: Cx26, Cx32, Cx33, Cx37 and Cx43. Immunocytochemical studies have shown that Cx43 assembles gap junctions between Leydig cells. The present study investigated the expression and regulation of the Cx43 gene in rat Leydig cells. Purified Leydig cells were obtained from 40-to 80-day-old Sprague-Dawley rats using a combination of arterial perfusion, collagenase digestion, centrifugal elutriation and Percoll gradient centrifugation. Leydig cells from 20-and 30-day-old rats were isolated without arterial perfusion or centrifugal elutriation. Cx43 mRNA was present in 20-day-old rat Leydig cells, reached a plateau at day 40, and remained at high levels in 65-and 80-day-old rat Leydig cells. To evaluate the regulation of Cx43 gene expression, Leydig cells were cultured overnight and then treated with human chorionic gonadotropin (hCG) for variable periods of time. Addition of hCG (10 ng/ml) increased cytochrome P450 side-chain cleavage and steroidogenic acute regulatory protein mRNA levels and testosterone formation. However, Cx43 mRNA levels were inhibited by hCG in a time-and dose-dependent manner. Cx43 mRNA levels decreased 27% as early as 2 h after the addition of hCG and decreased 60% by 24 h. Treatment of Leydig cells with 8-bromo-cAMP (0·1 mM) for 6 and 24 h also reduced Cx43 mRNA levels by 36 and 56% respectively. Primary cultured Leydig cells stained strongly positive with anti-Cx43 monoclonal antibody. Treatment with hCG for 24 h reduced Cx43 signals and caused Cx43 to redistribute to the periphery of the cells. To evaluate the regulation of Cx43 in vivo, rats were treated with hCG (300 ng i.p.) and testes were removed 24 h later. Frozen section of testes revealed that these interstitial cells stained positive for 3 -hydroxysteroid dehydrogenase (3 -HSD) by histochemical staining and were positive for Cx43 by immunofluorescence staining. The adjacent seminiferous tubules stained only weakly positive for Cx43. Twentyfour hours after hCG treatment, 3 -HSD activity increased while Cx43 immunostaining of Leydig cells was reduced. In conclusion, gap junction channels of Leydig cells are regulated by hCG both in vivo and in vitro. hCG increased Leydig cell steroidogenesis and steroidogenic enzyme mRNA levels but caused a redistribution of Cx43.

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Transcription of the gene for the gap junctional protein connexin43 and expression of functional cell-to-cell channels are regulated by cAMP.

Cited by 93 publications

References 39 publications

The bystander effect in the HSVtk/ganciclovir system and its relationship to gap junctional communication

The bystander effect in the HSVtk/ganciclovir system and its relationship to gap junctional communication

Expression of connexin 43 and gap junctional intercellular communication in the cumulus–oocyte complex in sheep

Expression and regulation of connexin43 in rat Leydig cells

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