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Author : Robert D. Loberg
Release : 2003
Genre :
Kind : eBook
Book Rating : /5 ( reviews)
Book Synopsis Role of Glycogen Synthase Kinase 3 Iin the Regulation of Vascular Smooth Muscle Cell Glucose Transport and Function by : Robert D. Loberg
Download or read book Role of Glycogen Synthase Kinase 3 Iin the Regulation of Vascular Smooth Muscle Cell Glucose Transport and Function written by Robert D. Loberg. This book was released on 2003. Available in PDF, EPUB and Kindle. Book excerpt:
Author : Anthony P. Popkie
Release : 2011
Genre :
Kind : eBook
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Book Synopsis Glycogen Synthase Kinase-3 Loss-of-function Studies in Mus Musculus and Murine Embryonic Stem Cells by : Anthony P. Popkie
Download or read book Glycogen Synthase Kinase-3 Loss-of-function Studies in Mus Musculus and Murine Embryonic Stem Cells written by Anthony P. Popkie. This book was released on 2011. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: Glycogen synthase kinase-3 (Gsk-3) isoforms, Gsk-3[alpha] and Gsk-3[beta], are constitutively active, largely inhibitory serine/threonine kinases that are involved in diverse cellular pathways ranging from Wnt signaling and insulin signaling to the maintenance of pluripotency in embryonic stem cells and neural progenitors. Underscoring their biological significance, altered Gsk-3 activity has been implicated in diabetes, cancer, Alzheimer's disease, schizophrenia, and bipolar disorder. Gsk-3 isoforms show gross functional redundancy in many cellular contexts including cultured embryonic stem cells (ESC) and neural progenitors. However, the consequences of genetic deletion are not equivalent for each isoform in vivo, while Gsk-3[alpha] null mice are viable, Gsk-3[beta] null mice are embryonic lethal. The presence of two distinct Gsk-3 isoforms is evolutionarily conserved throughout vertebrate species, and the distinct phenotypes of Gsk-3[alpha] and Gsk-3[beta] null mice suggest unique functions for each isoform. This work was designed to test the hypothesis that Gsk-3[alpha] and Gsk-3[beta] have unique functions in the regulation of downstream transcriptional targets. In order to explore these potentially distinct functions, we carried out genome-wide gene expression analysis in Gsk-3[alpha]-/-, Gsk-3[beta]-/-, and Gsk-3[alpha]-/- Gsk-3[beta]-/- double knockout (DKO) ESCs. We found that Gsk-3[alpha] and Gsk-3[beta] are essentially redundant in the context of the regulation of gene expression in cultured ESCs. However, we found a large number of genes are misregulated in the absence of both isoforms, many of which have not been previously linked with Gsk-3. In addition, we have also generated Gsk-3[alpha] and Gsk-3[beta] conditional knockout (CKO) mice in order to understand the distinct functions of Gsk-3 isoforms in vivo. We have shown that these conditional alleles are functional, and that Gsk-3[alpha]-/- and Gsk-3[beta]-/- mice derived from our CKO lines concur with previously reported phenotypes in conventional knockout mice. In the course of our studies, we have also discovered a novel role for Gsk-3 isoforms in the regulation of DNA methylation at imprinted loci. We found that deletion of both Gsk-3[alpha] and Gsk-3[beta] in mouse embryonic stem cells (ESCs), resulted in reduced expression of the de novo DNA methyltransferase Dnmt3a2, causing misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs and neural stem cells with the Gsk-3 inhibitor, lithium, phenocopies the DNA hypomethylation defect at imprinted loci. We show that phosphorylation and inhibition of Gsk-3 isoforms via activation of phosphoinositide 3-kinase (PI3K) also results in reduced DNA methylation. Finally, we find N-Myc is a potent Gsk-3-dependent regulator of Dnmt3a2 expression. In summary, we have identified a signal transduction pathway that is capable of altering DNA methylation at imprinted loci.
Author : Ana Martinez
Release : 2006-10-20
Genre : Science
Kind : eBook
Book Rating : 015/5 ( reviews)
Book Synopsis Glycogen Synthase Kinase 3 (GSK-3) and Its Inhibitors by : Ana Martinez
Download or read book Glycogen Synthase Kinase 3 (GSK-3) and Its Inhibitors written by Ana Martinez. This book was released on 2006-10-20. Available in PDF, EPUB and Kindle. Book excerpt: Many researchers believe that GSK-3 and its inhibitors could lead to effective treatments for neurogenerative disorders, type II diabetes, depression and bipolar disorder, and some forms of cancer. This book provides a thorough introduction to GSK-3, presents up-to-date information, and mentions the birth of several chemical families of GSK-3 inhibitors with varying selectivity. It’s a great reference for researchers in drug design and development.
Author : Morgan M. Brooks
Release : 2014
Genre :
Kind : eBook
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Book Synopsis The Role of Glycogen Synthase Kinase-3[beta] in the Regulation of Mitochondrial Membrane Permeability by : Morgan M. Brooks
Download or read book The Role of Glycogen Synthase Kinase-3[beta] in the Regulation of Mitochondrial Membrane Permeability written by Morgan M. Brooks. This book was released on 2014. Available in PDF, EPUB and Kindle. Book excerpt: Lens epithelial cells in a fully mature lens thrive in a hypoxic environment by developing several pro-survival mechanisms that can prevent cellular dysfunction. Many of these mechanisms focus on maintaining mitochondrial membrane integrity. Loss of integrity of either the inner or outer mitochondrial membrane results in the dissipation of the mitochondrial electrochemical gradient in a process termed mitochondrial membrane permeability transition (mMPT). The project herein focuses primarily on understanding the role of glycogen synthase kinase-3β (GSK-3β) in preventing mMPT in human lens epithelial (HLE-B3) cells; and, understanding that role in relation to extracellular signal-regulated kinase 1/2 (ERK1/2), a known regulator of GSK-3β activity. These studies further define mitoprotective mechanisms of lens cells by identifying how ERK1/2 and GSK-3β can directly (through the mitochondrial transition pore) or indirectly (through the induction of apoptosis) effect mitochondrial membrane potential). Additionally, we extended the GSK-3β studies into the field of epithelial to mesenchymal transition (EMT) research. Specifically we focused on understanding how GSK-3β in conjunction with the hypoxia inducible factor (HIF) proteins can influence the persistence of EMT and the production of vascular endothelial growth factor (VEGF). Collectively, these studies demonstrate important roles in lens epithelial cell mitoprotection for GSK-3β and ERK1/2; and, demonstrate a pivotal role for HIF-1α in the persistence of EMT under hypoxic conditions. Overall, the work described herein has provided invaluable information and understanding in the field of mitoprotection research as well as EMT research.
Author : Camila Rubio Patiño
Release : 2013
Genre :
Kind : eBook
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Book Synopsis Functional Role of Glycogen Synthase Kinase-3[beta] on Glucocorticoid-mediated Signaling by : Camila Rubio Patiño
Download or read book Functional Role of Glycogen Synthase Kinase-3[beta] on Glucocorticoid-mediated Signaling written by Camila Rubio Patiño. This book was released on 2013. Available in PDF, EPUB and Kindle. Book excerpt: Fundamental biological processes such as morphogenesis, tissue regeneration, and cancer invasion, depend on the collective migration of cell groups. The mechanisms that result in collective migration are not well understood, partially because the physical forces that initiate and maintain collective cell migration remain largely unknown. These forces include the traction forces, exerted by the cells on the extracellular matrix, and the cell-cell forces, transmitted between adjacent cells through cell-cell junctions. While the former have been studied, the latter have never been measured in the context of collective cell migration. The objective of this thesis has been to study these forces and integrate them in order to define the biomechanical mechanisms involved in the expansion of an epithelial monolayer. The thesis is presented as a compilation of two articles. In the first article, a new method for measuring intra-and intercellular forces in a cell monolayer was reported. It was shown that cells tend to align and migrate in the direction of maximal principal stress, demonstrating that intercellular forces act as a guidance mechanism during collective cell migration. In the second article, the expansion of an epithelial monolayer was studied. A new experimental model based on a barrier migration assay using polydimethylsiloxane membranes was implemented, allowing the study of epithelial expansion in a controlled and systematic manner. Structural and morphological changes at the cell level were observed during the expansion of the cellular monolayer. Furthermore, a mechanical wave propagates slowly spanning the entire monolayer, traversing intercellular junctions in a cooperative manner and building up differentials of mechanical stress. A minimal model based on sequential fronts of cytoskeletal reinforcement and fluidization captured essential features of this wave generation and propagation. These findings established a mechanism of long-range cell guidance, symmetry breaking and pattern formation during monolayer expansion.
