Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown in a transgenic mouse line, in which 5.2 kb of the elastin promoter was linked to the reporter enzyme chloramphenicol acetyltransferase (CAT), that the highest levels of expression were found in embryonic lungs and aorta, while lower levels were detected in other elastin-containing tissues. Furthermore, in general, expression of the transgene showed developmental regulation similar to that of the endogenous gene. However, the precise location of cellular expression could not be determined in this model. To overcome this limitation, we have developed a similar model, but replaced CAT with the reporter enzyme beta-galactosidase. Enzyme activity was readily detected in the transgenic mouse embryos in expected regions of tissue forming elastic fibers, including the dermis and elastic cartilage. Of considerable interest, however, was the novel finding of expression in specific areas of neuroepithelium of the brain and in the perichondrium surrounding areas destined to form hyaline cartilage in endochondral bone formation. These latter areas included all the bones of the limbs, the spine and rib cage. It appeared that these segments of elastin expression demarcated the border between the developing cartilage and the surrounding mesenchymal tissue. Elastin promoter expression was also found in developing somites, in the mesenchymal layer of the forming cornea of the eye, in the genital tubercle and in the epithelium destined to form the olfactory epithelium. These findings indicate that the elastin promoter is activated during embryonic development in a variety of tissues, suggesting that elastin gene expression may play a role in organizing cutaneous, skeletal and neural structures.
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PMID:Expression of the elastin promoter in novel tissue sites in transgenic mouse embryos. 1076 40

We describe the clinical findings, and the molecular and biochemical studies in an Italian family with recurrent hydrops fetalis due to galactosialidosis (GS). GS is a rare lysosomal storage disorder caused by a deficiency of the protective protein/cathepsin A (PPCA). This protein forms a high-molecular-weight complex with the hydrolases beta-galactosidase (GLB1) and neuraminidase (NEU1). By virtue of this association these two enzymes are correctly compartmentalized in lysosomes and protected against rapid proteolytic degradation. Controversial data show that PPCA is also present in a second complex, including the Elastin Binding Protein (EBP) the EBP-receptor, which is involved in elastogenesis, and NEU1. We investigated the potential role of the PPCA in both complexes. Two new genetic lesions (c60delG and IVS2+1 G > T) that lead to a frameshift and a premature stop codon were detected in the PPCA cDNA and genomic DNA of the patient. The deleterious effect of such mutations was confirmed by the complete absence of the PPCA protein on Western blots. Thus, we examined the effect of the loss of PPCA on the two protein complexes in the patient's fibroblasts. Interestingly, a reduced amount of both GLB1 and EBP proteins was detected. These data confirm that PPCA is present in two functional complexes one with GLB1 and NEU1 in the lysosomal lumen and the other with EBP at the cell surface. The reduction in GLB1 and EBP confirms that PPCA is essential for their integrity.
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PMID:New mutations in the PPBG gene lead to loss of PPCA protein which affects the level of the beta-galactosidase/neuraminidase complex and the EBP-receptor. 1511 Mar 21

Impaired elastic fiber assembly constitutes one major problem in skin wound healing. Recent data indicate that a ternary complex involving a splicing form of beta-galactosidase associated with cathepsin-A and neuraminidase-1 directs the transport of tropoelastin to the fibroblast plasma membrane and participates in the deposition of the elastin precursor onto a microfibrillar scaffold. In addition, this elastin receptor complex is ubiquitously expressed and also acts as a true receptor for elastin-derived peptides produced during the initial stage of wound repair following elastase-mediated proteolysis action. Among the peptides generated, those having a x.G.x.x.P.G. motif upregulate (i) keratinocyte migration, (ii) endothelial cell angiogenic phenotype, (iii) fibroblast proliferation, and (iv) induction of the expression of matrix metalloproteinases, type I collagen, and tropoelastin. All of these properties could accelerate the different stages of wound repair. Elastin-derived peptides from a chemical or a proteolytic digest of insoluble elastin alone or linked to the collagen scaffold significantly improve skin wound healing and dermal regeneration in vivo in several animal models. Such a beneficial influence has been recently extended to the treatment of burn patients. In this respect, recent investigations have focused on the design of elastin-derived peptides or elastin-building blocks, as obtained from peptide chemistry or by genetic engineering, to elaborate biocompatible elastin peptides, which are considered as ideal biomaterials for "catalyzing" skin repair and regeneration following injury.
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PMID:Role of the elastin receptor complex (S-Gal/Cath-A/Neu-1) in skin repair and regeneration. 1976 16