This study compared the effects of benzo(a)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), two aryl hydrocarbon receptor agonists, on cell attachment and adherens junction proteins in RL95-2 human uterine endometrial cells. Exposure to 10 microM BaP significantly decreased cell attachment to Matrigel, whereas 10 nM TCDD had no effect. Immunocytochemistry and Western immunoblot analysis showed that BaP, but not TCDD, produced a marked loss of plasma membrane epidermal growth factor receptor (EGF-R) localized along intercellular boundaries. BaP-treated cells exhibited significant decreases in beta-catenin and cadherin protein levels, while vinculin levels remained unchanged relative to control. In contrast, TCDD treatment had no effect on the levels of beta-catenin, cadherin, or vinculin. Further studies using the fluorescein labeled peptide phalloidin showed the presence of continuous subcortical actin filaments in control cells, whereas BaP-treated cells had subcortical actin aggregates. Thus, in contrast to TCDD, BaP produces a loss of cell attachment involving decreased localization of molecules important for cell-cell interactions in RL95-2 cells.
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http://dx.doi.org/10.1016/S0006-291X(02)00437-0 | DOI Listing |
Toxicol Appl Pharmacol
January 2025
Drug Safety Research & Development, Pfizer, Inc., Groton, CT 06340, USA.
One of the potential risk factors of recombinant adeno-associated virus (rAAV)-based gene therapy is insertional mutagenesis, which has been associated with the development of hepatocellular carcinoma (HCC) in rAAV-treated neonatal mice. The objective of this study was to investigate if well-established in vitro cell transformation assays (CTA) in mouse cell lines can detect AAV2 or AAVdj-mediated cell transformation. Since AAV integration at the Rian locus in neonatal mice has been implicated in AAV-mediated HCC, an rAAV vector specifically targeting the mouse Rian locus and an additional rAAV vector previously shown to cause HCC in neonatal mice were both tested for the induction of cell transformation in NIH3T3 cells.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Department of Molecular and Cellular Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan; Department of Clinical Bioanalysis and Molecular Biology, Graduate School of Medical and Dental Sciences, Institute Science of Tokyo/TMDU, Tokyo, Japan. Electronic address:
Myelin is an electrical insulator that enables saltatory nerve conduction and is essential for proper functioning of the central nervous system (CNS). It is formed by oligodendrocytes (OLs) in the CNS, and during OL development various molecules, including extracellular matrix (ECM) proteins, regulate OL differentiation and myelination; however, the role of ECM proteins in these processes is not well understood. Our present work is centered on the analyses of the expression and function of fibulin-7 (Fbln7), an ECM protein of the fibulin family, in OL differentiation.
View Article and Find Full Text PDFPoult Sci
January 2025
Institute of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan. Electronic address:
Escherichia coli (E. coli) is a widely distributed pathogenic bacterium that poses a substantial hazard to poultry, leading to the development of a severe systemic disease known as colibacillosis. Colibacillosis is involved in multimillion-dollar losses to the poultry industry each year worldwide.
View Article and Find Full Text PDFAntimicrob Agents Chemother
January 2025
Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Peptide-based therapeutics are gaining attention for their potential to target various viral and host cell factors. One notable example is Pep19-2.5 (Aspidasept), a synthetic anti-lipopolysaccharide peptide that binds to heparan sulfate proteoglycans (HSPGs) and has demonstrated inhibitory effects against certain bacteria and enveloped viruses.
View Article and Find Full Text PDFMethods Mol Biol
January 2025
Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
The soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) protein complex drives membrane fusion, and this process is further aided by accessory proteins, including complexin and α-synuclein. To understand the molecular mechanism underlying membrane fusion, we introduce an all-atom molecular dynamics (MD) simulation method. This method is used to understand and predict the conformations of protein and lipids, membrane geometry, and their interaction at femtosecond precision, by describing complex chemical systems with atomic models.
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