The Experts below are selected from a list of 14943 Experts worldwide ranked by ideXlab platform
Isabelle Plante - One of the best experts on this subject based on the ideXlab platform.
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from the cover exposure to an environmentally relevant mixture of brominated flame retardants decreased p β cateninser675 expression and its interaction with e cadherin in the Mammary Glands of lactating rats
Toxicological Sciences, 2017Co-Authors: Elham Dianati, Michael G Wade, Barbara F Hales, Bernard Robaire, Isabelle PlanteAbstract:Proper Mammary gland development and function require precise hormonal regulation and bidirectional cross talk between cells provided by means of paracrine factors as well as intercellular junctions; exposure to environmental endocrine disruptors can disturb these processes. Exposure to one such family of chemicals, the brominated flame retardants (BFRs), is ubiquitous. Here, we tested the hypothesis that BFR exposures disrupt signaling pathways and intercellular junctions that control Mammary gland development. Before mating, during pregnancy and throughout lactation, female Sprague-Dawley rats were fed diets containing that BFR mixture based on house dust, delivering nominal exposures of BFR of 0 (control), 0.06, 20, or 60 mg/kg/d. Dams were euthanized and Mammary Glands collected on postnatal day 21. BFR exposure had no significant effects on Mammary gland/body weight ratios or the levels of proteins involved in milk synthesis, epithelial-mesenchymal transition, cell-cell interactions, or hormone signalling. However, BFR exposure (0.06 mg/kg/d) down-regulated phospho-ser675 β-catenin (p-β-catSer675) levels in the absence of any effect on total β-catenin levels. Levels of p-CREB were also down-regulated, suggesting that PKA inhibition plays a role. p-β-catSer675 co-localized with β-catenin at the Mammary epithelial cell membrane, and its expression was decreased in animals from the 0.06 and 20 mg/kg/d BFR treatment groups. Although β-Catenin signaling was not affected by BFR exposure, the interaction between p-β-catSer675 and E-cadherin was significantly reduced. Together, our results demonstrate that exposure to an environmentally relevant mixture of BFR during pregnancy and lactation decreases p-β-catser675 at cell adhesion sites, likely in a PKA-dependant manner, altering Mammary gland signaling.
Elham Dianati - One of the best experts on this subject based on the ideXlab platform.
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from the cover exposure to an environmentally relevant mixture of brominated flame retardants decreased p β cateninser675 expression and its interaction with e cadherin in the Mammary Glands of lactating rats
Toxicological Sciences, 2017Co-Authors: Elham Dianati, Michael G Wade, Barbara F Hales, Bernard Robaire, Isabelle PlanteAbstract:Proper Mammary gland development and function require precise hormonal regulation and bidirectional cross talk between cells provided by means of paracrine factors as well as intercellular junctions; exposure to environmental endocrine disruptors can disturb these processes. Exposure to one such family of chemicals, the brominated flame retardants (BFRs), is ubiquitous. Here, we tested the hypothesis that BFR exposures disrupt signaling pathways and intercellular junctions that control Mammary gland development. Before mating, during pregnancy and throughout lactation, female Sprague-Dawley rats were fed diets containing that BFR mixture based on house dust, delivering nominal exposures of BFR of 0 (control), 0.06, 20, or 60 mg/kg/d. Dams were euthanized and Mammary Glands collected on postnatal day 21. BFR exposure had no significant effects on Mammary gland/body weight ratios or the levels of proteins involved in milk synthesis, epithelial-mesenchymal transition, cell-cell interactions, or hormone signalling. However, BFR exposure (0.06 mg/kg/d) down-regulated phospho-ser675 β-catenin (p-β-catSer675) levels in the absence of any effect on total β-catenin levels. Levels of p-CREB were also down-regulated, suggesting that PKA inhibition plays a role. p-β-catSer675 co-localized with β-catenin at the Mammary epithelial cell membrane, and its expression was decreased in animals from the 0.06 and 20 mg/kg/d BFR treatment groups. Although β-Catenin signaling was not affected by BFR exposure, the interaction between p-β-catSer675 and E-cadherin was significantly reduced. Together, our results demonstrate that exposure to an environmentally relevant mixture of BFR during pregnancy and lactation decreases p-β-catser675 at cell adhesion sites, likely in a PKA-dependant manner, altering Mammary gland signaling.
James J Tomasek - One of the best experts on this subject based on the ideXlab platform.
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myoepithelial cell contraction and milk ejection are impaired in Mammary Glands of mice lacking smooth muscle alpha actin
Biology of Reproduction, 2011Co-Authors: Carol J Haaksma, James J TomasekAbstract:Mammary myoepithelial cells are specialized smooth musclelike epithelial cells that express the smooth muscle actin isoform: smooth muscle alpha-actin (ACTA2). These cells contract in response to oxytocin to generate the contractile force required for milk ejection during lactation. It is believed that ACTA2 contributes to myoepithelial contractile force generation; however, this hypothesis has not been directly tested. To evaluate the contribution of ACTA2 to Mammary myoepithelial cell contraction, Acta2 null mice were utilized and milk ejection and myoepithelial cell contractile force generation were evaluated. Pups suckling on Acta2 null dams had a significant reduction in weight gain starting immediately postbirth. Cross-fostering demonstrated the lactation defect is with the Acta2 null dams. Carmine alum whole mounts and conventional histology revealed no underlying structural defects in Acta2 null Mammary Glands that could account for the lactation defect. In addition, myoepithelial cell formation and organization appeared normal in Acta2 null lactating Mammary Glands as evaluated using an Acta2 promoter-GFP transgene or phalloidin staining to visualize myoepithelial cells. However, Mammary myoepithelial cell contraction in response to oxytocin was significantly reduced in isolated Acta2 null lactating Mammary Glands and in in vivo studies using Acta2 null lactating dams. These results demonstrate that lack of ACTA2 expression impairs Mammary myoepithelial cell contraction and milk ejection and suggests that ACTA2 expression in Mammary myoepithelial cells has the functional consequence of enhancing contractile force generation required for milk ejection.
James L. Mcmanaman - One of the best experts on this subject based on the ideXlab platform.
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adipophilin regulates maturation of cytoplasmic lipid droplets and alveolae in differentiating Mammary Glands
Journal of Cell Science, 2011Co-Authors: Tanya D. Russell, David J. Orlicky, Carol A. Palmer, Benny Hung-junn Chang, Lawrence Chan, Jerome Schaack, James L. McmanamanAbstract:Milk lipids originate by secretion of triglyceride-rich cytoplasmic lipid droplets (CLDs) from Mammary epithelial cells. Adipophilin (ADPH)/Plin2, a member of the perilipin family of CLD binding proteins, is hypothesized to regulate CLD production in these cells during differentiation of the Mammary gland into a secretory organ. We tested this hypothesis by comparing CLD accumulation in differentiating Mammary Glands of wild-type and ADPH-deficient mice. ADPH deficiency did not prevent CLD formation; however, it disrupted the increase in CLD size that normally occurs in differentiating Mammary epithelial cells. Failure to form large CLDs in ADPH-deficient mice correlated with localization of adipose triglyceride lipase (ATGL) to the CLD surface, suggesting that ADPH promotes CLD growth by inhibiting lipolytic activity. Significantly, Mammary alveoli also failed to mature in ADPH-deficient mice, and pups born to these mice failed to survive. The possibility that CLD accumulation and alveolar maturation defects in ADPH-deficient mice are functionally related was tested by in vivo rescue experiments. Transduction of Mammary Glands of pregnant ADPH-deficient mice with adenovirus encoding ADPH as an N-terminal GFP fusion protein prevented ATGL from localizing to CLDs and rescued CLD size and alveolar maturation defects. Collectively, these data provide direct in vivo evidence that ADPH inhibition of ATGL-dependent lipolysis is required for normal CLD accumulation and alveolar maturation during Mammary gland differentiation. We speculate that impairing CLD accumulation interferes with alveolar maturation and lactation by disrupting triglyceride homeostasis in Mammary epithelial cells.
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Mammary Glands of adipophilin-null mice produce an amino-terminally truncated form of adipophilin that mediates milk lipid droplet formation and secretion.
Journal of lipid research, 2007Co-Authors: Tanya D. Russell, David J. Orlicky, Carol A. Palmer, Elise S. Bales, Benny Hung-junn Chang, Lawrence Chan, James L. McmanamanAbstract:Adipophilin (ADPH), a member of the perilipin family of lipid droplet-associated proteins, is hypothesized to mediate milk lipid formation and secretion. Unexpectedly, the fat content of milk from ADPH-null mice was only modestly lower than that of wild-type controls, and neither TIP47 nor perilipin appeared to fully compensate for ADPH loss. This prompted us to investigate the possibility that the mutated ADPH gene was not a genuine null mutation. ADPH transcripts were detected in ADPH-null Mammary tissue by quantitative real-time PCR, and C-terminal-specific, but not N-terminal-specific, ADPH antibodies detected a single lower molecular weight product and immunostained cytoplasmic lipid droplets (CLDs) and secreted milk fat globules in ADPH-null Mammary tissue. Furthermore, stable cell lines expressing cDNA constructs corresponding to the ADPH-null mutation produced a product comparable in size to the one detected in ADPH-null Mammary Glands and localized to CLDs. Based on these data, we conclude that ADPH-null mice express an N-terminally truncated form of ADPH that retains the ability to promote the formation and secretion of milk lipids.
Tanya D. Russell - One of the best experts on this subject based on the ideXlab platform.
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adipophilin regulates maturation of cytoplasmic lipid droplets and alveolae in differentiating Mammary Glands
Journal of Cell Science, 2011Co-Authors: Tanya D. Russell, David J. Orlicky, Carol A. Palmer, Benny Hung-junn Chang, Lawrence Chan, Jerome Schaack, James L. McmanamanAbstract:Milk lipids originate by secretion of triglyceride-rich cytoplasmic lipid droplets (CLDs) from Mammary epithelial cells. Adipophilin (ADPH)/Plin2, a member of the perilipin family of CLD binding proteins, is hypothesized to regulate CLD production in these cells during differentiation of the Mammary gland into a secretory organ. We tested this hypothesis by comparing CLD accumulation in differentiating Mammary Glands of wild-type and ADPH-deficient mice. ADPH deficiency did not prevent CLD formation; however, it disrupted the increase in CLD size that normally occurs in differentiating Mammary epithelial cells. Failure to form large CLDs in ADPH-deficient mice correlated with localization of adipose triglyceride lipase (ATGL) to the CLD surface, suggesting that ADPH promotes CLD growth by inhibiting lipolytic activity. Significantly, Mammary alveoli also failed to mature in ADPH-deficient mice, and pups born to these mice failed to survive. The possibility that CLD accumulation and alveolar maturation defects in ADPH-deficient mice are functionally related was tested by in vivo rescue experiments. Transduction of Mammary Glands of pregnant ADPH-deficient mice with adenovirus encoding ADPH as an N-terminal GFP fusion protein prevented ATGL from localizing to CLDs and rescued CLD size and alveolar maturation defects. Collectively, these data provide direct in vivo evidence that ADPH inhibition of ATGL-dependent lipolysis is required for normal CLD accumulation and alveolar maturation during Mammary gland differentiation. We speculate that impairing CLD accumulation interferes with alveolar maturation and lactation by disrupting triglyceride homeostasis in Mammary epithelial cells.
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Mammary Glands of adipophilin-null mice produce an amino-terminally truncated form of adipophilin that mediates milk lipid droplet formation and secretion.
Journal of lipid research, 2007Co-Authors: Tanya D. Russell, David J. Orlicky, Carol A. Palmer, Elise S. Bales, Benny Hung-junn Chang, Lawrence Chan, James L. McmanamanAbstract:Adipophilin (ADPH), a member of the perilipin family of lipid droplet-associated proteins, is hypothesized to mediate milk lipid formation and secretion. Unexpectedly, the fat content of milk from ADPH-null mice was only modestly lower than that of wild-type controls, and neither TIP47 nor perilipin appeared to fully compensate for ADPH loss. This prompted us to investigate the possibility that the mutated ADPH gene was not a genuine null mutation. ADPH transcripts were detected in ADPH-null Mammary tissue by quantitative real-time PCR, and C-terminal-specific, but not N-terminal-specific, ADPH antibodies detected a single lower molecular weight product and immunostained cytoplasmic lipid droplets (CLDs) and secreted milk fat globules in ADPH-null Mammary tissue. Furthermore, stable cell lines expressing cDNA constructs corresponding to the ADPH-null mutation produced a product comparable in size to the one detected in ADPH-null Mammary Glands and localized to CLDs. Based on these data, we conclude that ADPH-null mice express an N-terminally truncated form of ADPH that retains the ability to promote the formation and secretion of milk lipids.
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impaired tight junction sealing and precocious involution in Mammary Glands of pkn1 transgenic mice
Journal of Cell Science, 2007Co-Authors: Andreas Fischer, Tanya D. Russell, Heiko Stuckas, Markus Gluth, Michael C Rudolph, Neal E Beeman, Sebastian Bachmann, Shinobu Umemura, Yasuhiro Ohashi, Margaret C NevilleAbstract:The Mammary gland undergoes a complex set of changes to establish copious milk secretion at parturition. To test the hypothesis that signaling through the Rho pathway plays a role in secretory activation, transgenic mice expressing a constitutively activated form of the Rho effector protein PKN1 in the Mammary epithelium were generated. PKN1 activation had no effect in late pregnancy but inhibited milk secretion after parturition, diminishing the ability of transgenic dams to support a litter. Mammary gland morphology as well as increased apoptosis and expression of IFGBP5 and TGFβ3 suggest precocious involution in these animals. Furthermore, tight junction sealing at parturition was impaired in transgenic Mammary Glands as demonstrated by intraductal injection of [ 14 C]sucrose. Consistent with this finding, tight junction sealing in response to glucocorticoid stimulation was highly impaired in EpH4 Mammary epithelial cells expressing constitutively activated PKN1, whereas expression of a dominant-negative PKN1 mutant resulted in accelerated tight junction sealing in vitro. Tight junction formation was not impaired as demonstrated by the correct localization of occludin and ZO1 at the apical cell borders. Our results provide evidence that PKN1 participates in the regulation of tight junction sealing in the Mammary gland by interfering with glucocorticoid signaling.
