Effects of peroxisome proliferators and 12-O-tetradecanoyl phorbol-13-acetate on intercellular communication and connexin43 in two hamster fibroblast systems

Cruciani, Véronique; Mikalsen, Svein‐Ole; Vasseur, Paule; Sanner, Tore

doi:10.1002/(sici)1097-0215(19971009)73:2<240::aid-ijc14>3.0.co;2-j

Cited by 40 publications

(19 citation statements)

References 26 publications

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“…This view is further supported by a lack of correlation between the extent of Cx43 phosphorylation and degree of junctional uncoupling in this study (Figs. 4 and 6) and in others (49,77). Direct association of several proteins with Cx43 (78 -80) and probable involvement of protein-protein interaction in the regulation of Cx43-gap junctions (34,81) are in accord with our hypothesis.…”

Section: Discussionsupporting

confidence: 86%

“…This inhibition of GJC by the lipophilic U73122 is possibly due to its direct interaction with the membrane organelles, which is not mediated via Cx43 phosphorylation. Similar phosphorylation-independent inhibitory actions were observed with other lipophilic compounds such as octanol (47) and clofibrate (48,49). 2 Induction of MAPK was only slightly affected by U73122 treatment, further suggesting that Cx43 hyperphosphorylation requires participation of other signaling components downstream of PLC␥1 that are interfered by this compound.…”

Section: Resultssupporting

confidence: 57%

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Disruption of Gap Junctional Communication by the Platelet-derived Growth Factor Is Mediated via Multiple Signaling Pathways

Hossain

Jagdale

et al. 1999

Journal of Biological Chemistry

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The platelet-derived growth factor (PDGF) mediates its cellular functions via activation of its receptor tyrosine kinase followed by the recruitment and activation of several signaling molecules. These signaling molecules then initiate specific signaling cascades, finally resulting in distinct physiological effects. To delineate the PDGF signaling pathway responsible for the disruption of gap junctional communication (GJC), wild-type PDGF receptor ␤ (PDGFR␤) and a series of PDGFR␤ mutants were expressed in T51B rat liver epithelial cells. In cells expressing wild-type PDGFR␤, PDGF induced disruption of GJC and phosphorylation of a gap junctional protein, connexin-43 (Cx43), which required activation of mitogen-activated protein kinase, although involvement of additional factors was also evident. In the F5 mutant lacking binding sites for phosphatidylinositol 3-kinase, GTPase-activating protein, SHP-2, and phospholipase C␥1 (PLC␥1), PDGF induced mitogen-activated protein kinase, but failed to affect GJC or Cx43, indicating involvement of additional signals presumably initiated by one or more of the mutated binding sites. Examination of the single-site mutants revealed that PDGF effects were not mediated via a single signaling component. This was confirmed by the "add-back" mutants, which showed that restoration of either SHP-2 or PLC␥1 binding was sufficient to propagate the GJC inhibitory actions of PDGF. Further analysis showed that activation of PLC␥1 is involved in Cx43 phosphorylation, which surprisingly failed to correlate with GJC blockade. The results of our study demonstrate that PDGF-induced disruption of GJC can be mediated by multiple signaling pathways and requires participation of multiple components.

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Section: Discussionsupporting

confidence: 86%

Section: Resultssupporting

confidence: 57%

Disruption of Gap Junctional Communication by the Platelet-derived Growth Factor Is Mediated via Multiple Signaling Pathways

Hossain

Jagdale

et al. 1999

Journal of Biological Chemistry

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“…VIN effects had a transient character, which is similar to the transient inhibition of GJIC induced by TPA, EGF (Rivedal and Opsahl, 2001), lindane (Caruso et al, 2005), phenobarbital (Ruch and Klaunig, 1988) and other hepatic peroxisome proliferators (Cruciani et al, 1997). Restoration of GJIC, decrease in MAPK activity and Cx43 phosphorylation in this study coincided with the steady increase of M2 concentrations in the cell culture medium during the experiment, indicating an ongoing transformation of VIN into possibly less active products.…”

Section: Discussionsupporting

confidence: 74%

Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells

et al. 2016

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Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC 50 values for GJIC inhibition being 10 mM for MXC and 126 mM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC via mechanisms involving rapid activation of PC-PLC occurring independently of ER-or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors.

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“…Because V79 cells have low xenobiotic metabolism, Vang et al [196] used genetically engineered V79 cells that contained rat cytochrome P450s in metabolic cooperation assays, and at the only dose tested (78 mg/ml), reported a greater response in the parental strain than in those with increased CYP1A1, CYP1A2 or CYP2B1 expression. In the only available study of MEHP for GJIC, metabolic cooperation was inhibited at 28 mg/ml in Chinese hamster V79 cells after 3 days of incubation with decreased cell survival at 112 mg/ml [45]. In this same study, DEHP increased transformation at a much higher concentration (156 mg/ml) than other studies that have used this paradigm.…”

Section: Intercellular Communicationmentioning

confidence: 53%

DEHP: Genotoxicity and potential carcinogenic mechanisms—A review

Caldwell

2012

Mutation Research/Reviews in Mutation Research

185

101

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Effects of peroxisome proliferators and 12-O-tetradecanoyl phorbol-13-acetate on intercellular communication and connexin43 in two hamster fibroblast systems

Cited by 40 publications

References 26 publications

Disruption of Gap Junctional Communication by the Platelet-derived Growth Factor Is Mediated via Multiple Signaling Pathways

Disruption of Gap Junctional Communication by the Platelet-derived Growth Factor Is Mediated via Multiple Signaling Pathways

Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells

DEHP: Genotoxicity and potential carcinogenic mechanisms—A review

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