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)

Very early during the development of new pharmaceuticals toxicological tests are most important. In addition to acute and chronic toxicity tests, it is crucial to estimate the teratogenic potential of promising drugs. We established a simple biological test system based on the cellular slime mold Dictyostelium discoideum. Under certain environmental conditions single cells of D. discoideum aggregate and undergo a relatively simple cell differentiation program, leading to the formation of stalk and spore cells. Transgenic D. discoideum strains carrying the bacterial beta-galactosidase gene under the control of various developmentally regulated D. discoideum promoters were shown to be useful tools to test the teratogenic potential of valproic acid (VPA). This study describes the effects of the VPA analogues S-4-yn-VPA, R-4-yn-VPA, and 2-ethyl-4-pentynoic acid on the D. discoideum developmental system. The presence of S-4-yn-VPA during D. discoideum development resulted in a strong inhibition of spore cell differentiation, whereas stalk cell formation was less affected. The enantiomer R-4-yn-VPA as well as 2-ethyl-4-pentynoic acid had only moderate effects on D. discoideum development. The above results are consistent with data obtained in mammalian teratogenicity assays, and suggest that D. discoideum development should be investigated with a number of additional substances to provide a simple alternative for high throughput screenings of new drugs.
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PMID:Evaluation of the Teratogenic Potential of Valproic Acid Analogues in Transgenic Dictyostelium discoideum Strains. 2065 29

SmdA is a Dictyostelium orthologue of the SET/MYND chromatin re-modelling proteins. In developing structures derived from a null mutant for smdA (a smdA- strain), prestalk patterning is normal, but using a prespore lacZ reporter fusion, there is ectopic accumulation of beta-galactosidase in the prestalk region. As wild type slugs migrate, there is continual forward movement and re-differentiation of prespore cells into prestalk cells. Thus, a potential explanation for the ectopic reporter localization in smdA null prestalk cells is an increased rate of re-differentiation and anterior movement of prespore cells. In support of this notion, analysis of an unstable lacZ reporter, driven by the prespore promoter, reveals a normal staining pattern in the smdA- strain. We suggest that one or more genes regulated by SmdA acts to repress prespore re-specification.
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PMID:A SET/MYND chromatin re-modelling protein regulates Dictyostelium prespore patterning. 2167 Dec 23

Dictyostelium discoideum encodes a single Rheb protein showing sequence similarity to human homologues of Rheb. The DdRheb protein shares 52 percent identity and 100 percent similarity with the human Rheb1 protein. Fluorescence of Rheb yellow fluorescent protein fusion was detected in the D. discoideum cytoplasm. Reverse transcription-polymerase chain reaction and whole-mount in situ hybridization analyses showed that rheb is expressed at all stages of development and in prestalk cells in the multicellular structures developed. When the expression of rheb as a fusion with lacZ was driven under its own promoter, the beta-galactosidase activity was seen in the prestalk cells. D. discoideum overexpressing Rheb shows an increase in the size of the cell. Treatment of the overexpressing Rheb cells with rapamycin confirms its involvement in the TOR signalling pathway.
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PMID:Analysis of Rheb in the cellular slime mold Dictyostelium discoideum: cellular localization, spatial expression and overexpression. 2449 92


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