Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D03345 (beta-Galactosidase)
 434 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The GLN1 gene of Saccharomyces cerevisiae was cloned by complementation of a gln1 auxotroph. A GLN1-lacZ fusion was constructed to assay GLN1 promoter activity. beta-Galactosidase and glutamine synthetase expression in chromosomally integrated GLN1-lacZ fusion strains were co-regulated in response to a shift from glutamine to glutamate as the nitrogen source, purine limitation, and 3-aminotriazole-induced histidine starvation. Regulation of GLN1 expression by each of the three pathways occurred at the transcriptional level. Increased accumulation of GLN1 mRNA was observed within 5 min after a shift from glutamine to glutamate as the nitrogen source. After 5 min, GLN1 mRNA levels were constant. The level of GLN1 transcript was reduced by approximately 75% within 5 min following glutamine addition to the cells growing with glutamate as nitrogen source. This indicates that the GLN1 message is unstable and has a half-life of approximately 3 min. Deletion analysis indicated that the sequences required for GLN1 expression are located within approximately 350 bp upstream from the transcriptional initiation site.
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PMID:Three regulatory systems control expression of glutamine synthetase in Saccharomyces cerevisiae at the level of transcription. 257 Mar 48

Growth factors are considered pivotal for the development, maintenance, and function of mesencephalic dopaminergic neurons. Recent studies have identified a plethora of growth factors which support the survival and differentiation of embryonic dopaminergic neurons. However, the exact cellular targets of these growth factors, and, thus, their precise mechanisms of action, remain largely unknown. To identify these cellular targets, we analysed, at the single cell level, growth factor-induced c-fos expression in dissociated mesencephalic cell cultures derived from a fos-lac Z transgenic mouse line. Pharmacological interference with cell-cell communication was utilized to control for direct growth factor effects. beta-Galactosidase-expressing cells were phenotypically characterized by immunocytochemistry to specific neural cell markers. Glia cell line-derived neurotrophic factor, basic fibroblast growth factor, brain-derived neurotrophic factor, and neurotrophin-3 directly induced Fos expression in differently sized, yet overlapping, populations of tyrosine hydroxylase-immunoreactive dopaminergic neurons. In an additional subpopulation of dopaminergic neurons, neurotrophin-3 induced fos-lac Z expression indirectly through a glutamate-mediated activation of N-methyl-D-aspartate receptors. Consistent with their proposed glial-mediated mode of action, transforming growth factor alpha and platelet-derived growth factor induced Fos expression predominantly in glia but only in a very small number of dopaminergic neurons. These findings demonstrate that individual dopaminergic neurons represent the direct targets of different sets of extracellular growth factors. Our findings further establish that growth factors affect dopaminergic neurons by indirect mechanisms which require specific cell-cell communication. These data also suggest a potential role for growth factors in the establishment of the morphological and functional diversity of midbrain dopaminergic neurons.
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PMID:Growth factor-induced c-fos expression defines distinct subsets of midbrain dopaminergic neurons. 878 57

It was previously shown that MRG19 downregulates carbon metabolism in Saccharomyces cerevisiae upon glucose exhaustion, and that the gene is glucose repressed. Here, it is shown that glucose repression of MRG19 is overcome upon nitrogen withdrawal, suggesting that MRG19 is a regulator of carbon and nitrogen metabolism. beta-Galactosidase activity fostered by the promoter of GDH1/3, which encode anabolic enzymes of nitrogen metabolism, was altered in an MRG19 disruptant. As compared to the wild-type strain, the MRG19 disruptant showed a decrease in the ratio of 2-oxoglutarate to glutamate under nitrogen-limited conditions. MRG19 disruptants showed reduced pseudohyphal formation and enhanced sporulation, a phenomenon that occurs under conditions of both nitrogen and carbon withdrawal. These studies revealed that MRG19 regulates carbon and nitrogen metabolism, as well as morphogenetic changes, suggesting that MRG19 is a component of the link between the metabolic status of the cell and the corresponding developmental pathway.
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PMID:Disruption of MRG19 results in altered nitrogen metabolic status and defective pseudohyphal development in Saccharomyces cerevisiae. 1563 29

Glial cells are currently viewed as active partners of neurons in synapse formation. The close proximity of astrocytes to the synaptic cleft suggests that these cells might be potential targets for neuronal-released molecules although this issue has been less addressed. Here, we evaluated the role of the excitatory neurotransmitter, glutamate, in astrocyte differentiation. We recently demonstrated that cortical neurons activate the gene promoter of the astrocyte maturation marker, GFAP (glial fibrillary acidic protein) of cerebral cortex astrocytes by inducing TGF-beta1 (transforming growth factor beta 1) secretion in vitro. To access the effect of glutamate on GFAP gene, we used transgenic mice bearing the beta-Galactosidase (beta-Gal) reporter gene under the regulation of the GFAP gene promoter. We report that 100 muM glutamate activates the GFAP gene promoter of astrocytes from cerebral cortex revealed by a significant increase in the number of beta-Gal positive astrocytes. Neutralizing antibodies against TGF-beta completely prevented glutamate and neuronal-induction of GFAP gene, thus indicating that this event is mediated by TGF-beta1. Further, induction of GFAP gene in response to glutamate was followed by nuclear translocation of the Smad transcription factor, a hallmark of TGF-beta1 pathway activation. The antagonist of the metabotropic glutamate receptor, MCPG, inhibited neuronal effect suggesting that neuronal activation of GFAP gene promoter involves glutamate metabotropic receptors. MAPK (PD98059) and PI3K (LY294002) inhibitors fully prevented activation of GFAP gene promoter by all treatments. Surprisingly, these inhibitors also abrogated TGF-beta1 direct action on GFAP gene although they did not inhibit Smad-2 phosphorylation, suggesting that TGF-beta1-induced GFAP gene activation might involve cooperation between the canonical and non-canonical TGF-beta pathways. Together, our results suggest that glial metabotropic glutamate 2/3 receptor activation by neurons induces TGF-beta1 secretion, leading to GFAP gene activation and astrocyte differentiation and involves Smad and MAPK/PI3K pathways. Our work provides evidence that astrocytes surrounding synapses are target of neuronal activity and might shed light into the role of glial cells into neurological disorders associated with glutamate neurotoxicity.
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PMID:Glutamate activates GFAP gene promoter from cultured astrocytes through TGF-beta1 pathways. 3258 92