Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dystroglycan is a component of the dystrophin-glycoprotein complex (DGC) in muscle and a cell surface receptor for laminin. Numerous muscular dystrophies are the result of disruption of proteins comprising the DGC, but the underlying pathogenetic mechanisms are unknown. Because apoptosis is an early feature of muscular dystrophy in vivo, and perturbation of cell-extracellular matrix associations is known to induce apoptosis, we investigated the role of dystroglycan-laminin interactions in the propagation and maintenance of cell survival signals in muscle cells. We found that disrupting the interaction between alpha-dystroglycan and the extracellular matrix protein laminin induces apoptosis in muscle cells. This increase in apoptosis is mediated in part by caspase activation and can be blocked by a caspase-3 inhibitor. We demonstrate a role for the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway in muscle cell-survival signaling using a pharmacological inhibitor of PI3K. Treatment with this inhibitor resulted in decreased phosphorylation of AKT and its downstream effector glycogen synthase kinase (GSK)-3beta and induced apoptosis in muscle cell cultures. Disruption of dystroglycan-laminin interactions resulted in decreased phosphorylation of AKT and GSK-3beta. Furthermore, activation of AKT prior to the disruption of dystroglycan-laminin protected the muscle cells from the induction of apoptosis. These results support a role for the PI3K/AKT pathway in the propagation of cell-survival signals mediated by the DGC and provide new insight into the molecular pathogenesis associated with the development of muscular dystrophies.
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PMID:Inhibition of dystroglycan binding to laminin disrupts the PI3K/AKT pathway and survival signaling in muscle cells. 1240 86

Dystroglycan is a cell surface receptor involved in the pathogenesis of muscular dystrophy, and plays a critical role in the assembly and homeostasis of basement membranes. Since data about the amphibian homologue are limited, we have cloned the full-length dystroglycan cDNAs from the frog Xenopus laevis. Using in situ hybridization, we show that mRNA expression is dynamic, particularly in the notochord at the end of gastrulation and during neurulation, suggesting that the protein might play unexplored roles in the specification and/or formation of this tissue. Subsequently, the transcripts are detected in the otic vesicle, the developing brain, and in mesenchymal cells of the visceral arches, as well as in pharyngeal endoderm, the pronephros, pronephric ducts, proctodaeum and the somites.
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PMID:Cloning and expression patterns of dystroglycan during the early development of Xenopus laevis. 1273 43

Interaction of epithelial cells with basement membrane (BM) is mediated by cell-adhesion molecules, which regulate cell proliferation, motility, and differentiation by integrating signals from extracellular matrix and soluble factors. alpha-Dystroglycan (alpha-DG) is one of the most important adhesion molecules in epithelial cell-BM interaction. alpha-DG serves as the cell surface receptor for several major BM proteins, including laminin, perlecan, and agrin. The laminin G-like domain in all these proteins binds to a unique glycan structure, so-called laminin-binding glycan, attached to alpha-DG with high affinity. Formation of the laminin-binding glycan is required for the BM assembly, and loss or deficiency of the glycan causes muscular dystrophy. We studied the role of this alpha-DG-specific glycan modification in tumor development, and identified a tumor suppressor function of the laminin-binding alpha-DG. In this chapter, we describe methods used to isolate the cell populations from human prostate cancer cell line PC3 and characterize their potentials in tumor formation and metastasis in vitro and in vivo.
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PMID:A tumor suppressor function of laminin-binding alpha-dystroglycan. 2081 78