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Cytoskeletal Reorganization (cytoskeletal + reorganization)
Selected AbstractsReprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome,DEVELOPMENTAL DYNAMICS, Issue 2 2007Maia L. Green Abstract Fetal Alcohol Spectrum Disorders (FASD) are birth defects that result from maternal alcohol use. We used a non a priori approach to prioritize candidate pathways during alcohol-induced teratogenicity in early mouse embryos. Two C57BL/6 substrains (B6J, B6N) served as the basis for study. Dosing pregnant dams with alcohol (2× 2.9 g/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a higher incidence than B6N embryos. Counter-exposure to PK11195 (4 mg/kg) significantly protected B6J embryos but slightly promoted FASD in B6N embryos. Microarray transcript profiling was performed on the embryonic headfold 3 hr after the first maternal alcohol injection (GEO data series accession GSE1074). This analysis revealed metabolic and cellular reprogramming that was substrain-specific and/or PK11195-dependent. Mapping ethanol-responsive KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed down-regulation of ribosomal proteins and proteasome, and up-regulation of glycolysis and pentose phosphate pathway in B6N embryos; and significant up-regulation of tight junction, focal adhesion, adherens junction, and regulation of the actin cytoskeleton (and near-significant up-regulation of Wnt signaling and apoptosis) pathways in both substrains. Expression networks constructed computationally from these altered genes identified entry points for EtOH at several hubs (MAPK1, ALDH3A2, CD14, PFKM, TNFRSF1A, RPS6, IGF1, EGFR, PTEN) and for PK11195 at AKT1. Our findings are consistent with the growing view that developmental exposure to alcohol alters common signaling pathways linking receptor activation to cytoskeletal reorganization. The programmatic shift in cell motility and metabolic capacity further implies cell signals and responses that are integrated by the mitochondrial recognition site for PK11195. Developmental Dynamics 236:613,631, 2007. © 2007 Wiley-Liss, Inc. [source] Selective expression of the small GTPase RhoB in the early developing mouse lensDEVELOPMENTAL DYNAMICS, Issue 3 2001Rupalatha Maddala Abstract This report describes the expression and distribution pattern of RhoB GTPase in the developing mouse lens. RhoB expression was confirmed by sequencing an reverse transcriptase-polymerase chain reaction,generated DNA fragment of RhoB. Immunohistochemical analysis of RhoB revealed expression in the lens vesicle (both anterior and posterior vesicle) at embryonic day (E) 11.5, and in the epithelium and primary fibers of the E14.5 lens. Compared with the neonatal stage (day 1), where RhoB is detected in the entire lens (epithelium, primary, and secondary fibers), expression of this protein is restricted to the epithelial and outer cortical secondary fibers in postnatal lenses (from day 7 to day18). Interestingly, in E11.5 and E14.5 lenses, RhoB is localized predominantly in the lens, but not detectable in the retina, cornea, or other ocular tissues. RhoB expression appears to be down-regulated in the postnatal lens with concomitant up-regulation in the retina and cornea, compared with earlier stages of development (eyes of E11.5, E14.5, and neonatal mice). This study reveals the selective expression of RhoB in the lens during early eye development and suggests a potential role for this small GTPase in cytoskeletal reorganization associated with lens epithelial cell elongation and differentiation. © 2001 Wiley-Liss, Inc. [source] In GERD patients, mucosal repair associated genes are upregulated in non-inflamed oesophageal epitheliumJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5 2009D. R. De Vries Abstract Previous studies addressing the effects of acid reflux and PPI therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non-inflamed oesophageal epithelium of GERD patients. Therefore, we included 20 GERD patients with pathological total 24-hr acid exposure of 6,12% and SAP , 95%. Ten patients discontinued PPI treatment (PPI-), 10 took pantoprazole 40 mg bid (PPI+). Ten age/sex-matched healthy controls were recruited. Biopsies were taken from non-inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (SCJ). Gene expression profiling of biopsies from 6 cm was performed on Human Genome U133 Plus 2.0 arrays (Affymetrix). Genes exhibiting a fold change >1.4 (t-test P -value < 1E, 4) were considered differentially expressed. Results were confirmed by real-time RT-PCR. In PPI- patients, 92 microarray probesets were deregulated. The majority of the corresponding genes were associated with cell,cell contacts, cytoskeletal reorganization and cellular motility, suggesting facilitation of a migratory phenotype. Genes encoding proteins with anti-apoptotic or anti-proliferative functions or stress-protective functions were also deregulated. No probesets were deregulated in PPI+ patients. QPCR analysis of 20 selected genes confirmed most of the deregulations in PPI- patients, and showed several deregulated genes in PPI+ patients as well. In the biopsies taken at 16 cm QPCR revealed no deregulations of the selected genes. We conclude that upon acid exposure, oesophageal epithelial cells activate a process globally known as epithelial restitution: up-regulation of anti-apoptotic, anti-oxidant and migration associated genes. Possibly this process helps maintaining barrier function. [source] A novel functional role for the highly conserved , -subunit KVGFFKR motif distinct from integrin ,IIb,3 activation processesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2006K. AYLWARD Summary.,Background: The highly conserved integrin , -subunit membrane-proximal motif KVGFFKR plays a decisive role in modulating the activation of integrin ,IIb,3. Previously, we have shown that a platelet permeable palmityl (pal)-peptide with this seven amino acid sequence can directly activate ,IIb,3 leading to platelet aggregation. Objectives: To investigate further the role of the KVGFFKR motif in integrin ,IIb,3 function. Methods: We used two sequence-specific complementary model systems, palmityl pal-peptides in platelets, and mutant ,IIb,3 -expressing Chinese Hamster Ovary (CHO) cell lines. Results: In platelets we show that the two phenylalanine amino acids in pal-KVGFFKR (pal-FF) peptide are critical for stimulating platelet aggregation. Pal-FF peptide treatment of platelets also gives rise to a tyrosine phosphorylation signal despite the presence of inhibitors of fibrinogen binding. In CHO cells, a double alanine substitution, ,IIb(F992A, F993A),3, induces constitutive integrin activation but prevents actin stress fiber formation upon adhesion to fibrinogen, suggesting that ,IIb,3 -mediated cytoskeletal reorganization is also dependent on F992 and F993. This further highlights a critical role for the two phenylalanine residues in both of these ,IIb,3 -mediated processes. Conclusion: In addition to regulating integrin ,IIb,3 activation state, the KVGFFKR motif also influences cytoskeletal reorganization. This activity is critically determined by F992 and F993 within the seven amino acid sequence. [source] | ||||||||||