Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The existence of lysosomes and acid hydrolase activity was demonstrated in an in vitro blood-brain barrier (BBB) model comprising primary cultures of bovine brain microvessel endothelial cell (BMEC) monolayers. BMEC lysosomes were observed by the uptake of acridine orange and fluorophore-labeled acetylated low-density lipoprotein by fluorescence microscopy. Cytochemical localization of the acid hydrolase, sulfatase, and acid phosphatase (AcP) activities with light microscopy also revealed hydrolase-positive vacuoles or lysosomes that varied in number from cell to cell. BMEC monolayers were fractionated and biochemical assays of the sulfatase, AcP, and beta-galactosidase were performed. Significant activities of the acid hydrolases were found to be associated with lysosome and microsome fractions (69-77%). The majority of beta-galactosidase (approximately 48%) and total sulfatase (approximately 58%) activity was associated with the lysosome fraction of the BMECs. In contrast, approximately 52% of AcP activity was associated with the microsome fraction of the cells. The results of this study are consistent with the demonstration in vivo of acid hydrolases as potential factors in the endocytic pathway for transport of proteins through the BBB and as contributors to the BBB's enzymatic barrier function.
...
PMID:Demonstration of acid hydrolase activity in primary cultures of bovine brain microvessel endothelium. 249 11

We describe here the properties of a mutant of Chinese hamster ovary cells that expresses a conditional-lethal mutation affecting dense lysosomes. This mutant, termed V.24.1, is a member of the End4 complementation group of temperature-sensitive mutants selected for resistance to protein toxins (Colbaugh, P. A., C.-Y. Kao, S.-P. Shia, M. Stookey, and R. K. Draper. 1988. Somatic Cell Mol. Genet. 14:499-507). Vesicles present in postnuclear supernatants prepared from V.24.1 cells harvested at the restrictive temperature had a 50% reduction in acidification activity, assessed by the ATP-stimulated accumulation of the dye acridine orange in acidic vesicles. To investigate whether specific populations of vesicles were impaired in acidification, we measured acidification activity in three subcellular fractions prepared from Percoll gradients: one containing endosomal and Golgi markers, one containing buoyant lysosomes, and the third containing dense lysosomes. Activity in dense lysosomes was reduced by 90%, activity in the buoyant lysosome fraction was unaffected, and activity in the endosome-Golgi fraction was mildly reduced. The activity of three lysosomal enzymes--beta-hexosaminidase, beta-galactosidase, and beta-glucocerebrosidase--was also reduced in dense lysosomes but nearly normal in the buoyant lysosome fraction. However, beta-hexosaminidase and beta-glucocerebrosidase activity was increased two- to threefold in the endosome-Golgi fraction. We conclude that the lesion selectively impairs dense lysosomes but has little effect on properties of buoyant lysosomes.
...
PMID:Impaired lysosomes in a temperature-sensitive mutant of Chinese hamster ovary cells. 252 60

Activities of lysosomal enzymes acid phosphatase, N-acetyl-beta-D-glucosaminidase, beta-galactosidase, acid lipase and cathepsins B and D were studied after accumulation of neutral red, acridine orange chloroquine and daunorubicin in lysosomes of fibroblasts of the LSM substrain. All the drugs studied proved to be inhibitors of these enzymes except of daunorubicin, which stimulated acid lipase activity. Lysosomotropic drugs are considered as possible regulators of the activity of lysosomes.
...
PMID:[Lysosomotropic agents as regulators of the activity of lysosomal hydrolases]. 368 95

Kinetics of Neutral red (NR) and Acridine orange (AO) uptake by cultured L cells (subline LSM) has been studied. It was found that the uptake of both NR and AO, with their constant concentrations in the medium was characterized as a two-phase process. During 2 hours, these cells concentrated as much as 90% of the total amount of NR and AO taken up during the whole incubation period. The segregation and accumulation of NR, AO as well as NH4Cl took place in lysosomes. NR and AO concentrations within the cells exceed by 600 and 400 times, respectively, those in the medium. NR, AO and NH4+ accumulation in cells resulted in inhibition of the activity of the following lysosomal hydrolases: cathepsins B and D, acid lipase, N-acetyl-beta,D-glucosaminidase, beta-galactosidase, acid phosphatase and galactosyltransferase, the latter being a marker of Golgi apparatus. The effect of lysosomal enzyme activity inhibition on the cell economy, and a possible role of lysosomotropic agents as regulators of the lysosomal apparatus functional activity are discussed.
...
PMID:[Effect of the segregation of neutral red, acridine orange and ammonium chloride by L cells (subline LSM) on lysosomal hydrolase activity]. 376 7

16 lac frameshift mutants induced by an acridine derivative, ICR-191D, in E. coli are leaky for beta-galactosidase activity. Activities of all mutants differ from each other and from the wild type in their stability to thermal denaturation. The leakiness is under ribosomal control, since it is strongly reduced by strA restrictive mutations and is restored by ram mutations that reverse restriction. Addition of streptomycin during growth has an effect similar to the presence of the ram mutation. These ribosomal alterations do not modify the thermal stability of the enzyme.It is suggested that the leakiness is due to an infrequent 2- or 4-base reading close to the frameshift mutation site. The possibility that not only the ribosome, but also the reading context in the messenger, plays a role in securing code fidelity is discussed.
...
PMID:Low activity of -galactosidase in frameshift mutants of Escherichia coli. 455 57

Loss of lysosomal integrity is a critical event for killing tumor cells in the photodynamic therapy of cancers. To elucidate the mechanism of photodamage induced lysosomal disintegration, we investigated the role of losing lysosomal proton translocation in latency loss of photosensitized lysosomes. Isolated rat liver lysosomes were light exposed in the presence of Methylene blue. Through monitoring lysosomal delta pH with Acridine orange and measuring its membrane potential with 3,3'-dipropylthiadicarbocyanine iodide, loss of Mg-ATP dependent proton translocation and decrease in electrogenicity of the proton pump were observed after lysosomes were photosensitized. When normal lysosomes were incubated for 60 min in K+ contained medium, percentage free activity of lysosomal enzyme beta-galactosidase increased, i.e. lysosomal latency decreased. In the presence of Mg-ATP, the latency loss of incubated lysosomes reduced. Addition of n-ethylmaleimide, a potent inhibitor of lysosomal H(+)-ATPase, abolished the effect of Mg-ATP on lysosomal latency. It suggests a role of proton translocation in protecting lysosomal integrity. Under the same conditions, Methylene blue photosensitized lysosomes increasingly lost latency of beta-hexosaminidase and beta-galactosidase with light exposure, presumably due to the photodamage induced loss of proton pumping. In contrast, the photosensitization did not decrease lysosomal latency in the absence of Mg-ATP, implying that lysosomal integrity might not be impaired via other photodamage effects under the conditions of this study. These results indicate that lysosomal integrity can be photodestructed via the loss of proton translocation.
...
PMID:Loss of lysosomal integrity caused by the decrease of proton translocation in methylene blue-mediated photosensitization. 886 12

Progress in the field of osteoclast gene regulation has been hampered significantly by the lack of such cell lines. In this study, mouse osteoclast precursor cells were elicited in an osteoclast-inductive coculture system and immortalized using SV40 large T antigen. One of the osteoclast precursor cell lines (MOCP-5) forms 95% tartrate-resistant acid phosphatase positive (TRAP+) multinuclear osteoclast-like cells (OCLs) in the coculture system. The yield of TRAP+ OCLs was 4.5-7x10(4) cells per 10 cm2 dish. Expression of SV40 large T antigen was visualized in the nucleus of MOCP-5 cells and OCLs by immunohistochemistry. MOCP-5 cells were positive for MoMa-2 antigen and nonspecific esterase but negative for F4/80 antigen. OCLs derived from MOCP-5 cells were positive for able to form extensive resorption bone pits on bone slices. The resorbing activity of the OCLs was comparable to that of authentic mouse osteoclasts. Pit formation was inhibited by salmon calcitonin (CT). Acid production by OCLs was demonstrated by vital staining with acridine orange. The OCLs expressed cathepsin K and CT receptors. MOCP-5 cells could be transfected by a construct that carries the beta-galactosidase gene. Transfected MOCP-5 cells expressing beta-galactosidase retain the ability to differentiate into OCLs, indicating a useful model for osteoclast gene regulation. To date, the MOCP-5 cell line has been maintained in continuous culture for 23 months and has maintained the capacity to differentiate into osteoclasts throughout this time. In summary, these data show that a stable immortalized osteoclast precursor cell line has been established and that the immortalization with SV40 large T oncogene does not prevent osteoclast precursor cell differentiation.
...
PMID:Generation of mouse osteoclastogenic cell lines immortalized with SV40 large T antigen. 966 Oct 75

Previous reports have demonstrated the effectiveness of chitosan as a transfection agent. These studies have noted the importance of polysaccharide backbone interactions with the cell surface as well as cationic groups in the transfection process. The present study focuses upon the potential utility of another polysaccharide hydrogel, alginic acid, as a transfection agent. Alginic acid was modified by carbodiimide-mediated linkage of several heterocyclic and aromatic amines to the carboxyl group of the alginate, giving the alginate polycationic characteristics through which binding to nucleic acids could be facilitated. The amines used for this modification include diaminoacridine, thionin, basic fuchsin, acridine yellow, and diaminomethyltriazine. Of all the conjugates tested, basic fuchsin-modified alginate produced the greatest increase in the transfection of a plasmid coding for beta-galactosidase into HeLa cells. These studies demonstrate that other polysaccharide hydrogels can be used as transfection agents, and the structural orientation of the cationic spacer arm is crucial for effective transfection.
...
PMID:A preliminary investigation of modified alginates as a matrix for gene transfection in a HeLa cell model. 1185 1

The telomerase complex is responsible for telomere maintenance and represents a promising cancer therapeutic target. We describe herein the antitelomerase and antitumor properties of a small-molecule compound designed by computer modeling to interact with and stabilize human G-quadruplex DNA, a structure that may form with telomeric DNA, thereby inhibiting access to telomerase. The 3,6,9-trisubstituted acridine 9-[4-(N,N-dimethylamino)phenylamino]-3,6-bis(3-pyrrolodinopropionamido) acridine (BRACO19) represents one of the most potent cell-free inhibitors of human telomerase yet described (50% inhibitory concentration of 115 +/- 18 nM). Moreover, in contrast to G-quadruplex interactive agents described previously, BRACO19 did not cause nonspecific acute cytotoxicity at similar concentrations to those required to completely inhibit telomerase activity. There exists a 90-fold differential (mean 50% inhibitory concentration for acute cell kill across seven human tumor cell lines of 10.6 +/- 0.7 microM). The exposure of 21NT human breast cancer cells, which possess relatively short telomeres, to nonacute cytotoxic concentrations of BRACO19 (2 microM) resulted in a marked reduction in cell growth after only 15 days. This was concomitant with a reduction in intracellular telomerase activity and onset of senescence as indicated by an increase in the number of beta-galactosidase positive-staining cells. Intraperitoneal administration of nontoxic doses of BRACO19 (2 mg/kg) to mice bearing advanced stage A431 human vulval carcinoma subcutaneous xenografts and previously treated with paclitaxel induced a significant increase in antitumor effect compared with that observed with paclitaxel alone. BRACO19 thus represents the first of a "second generation" of G-quadruplex-mediated telomerase/telomere-interactive compounds. It possesses nanomolar potency against telomerase but low nonspecific cytotoxicity, growth inhibitory effects, and induction of senescence in a human breast cancer cell line and, moreover, significant antitumor activity in vivo when administered post paclitaxel to mice bearing a human tumor xenograft carcinoma.
...
PMID:A G-quadruplex-interactive potent small-molecule inhibitor of telomerase exhibiting in vitro and in vivo antitumor activity. 1196 Nov 34

Falkow, Stanley (Walter Reed Army Institute of Research, Washington, D.C.), J. A. Wohlhieter, R. V. Citarella, and L. S. Baron. Transfer of episomic elements to Proteus. I. Transfer of F-linked chromosomal determinants. J. Bacteriol. 87:209-219. 1964.-F-linked lac(+) genes may be transferred from Escherichia coli to several species of Proteus by conjugation. Usually the transferred genetic elements are markedly unstable in Proteus, but repeated plating permits the selection of relatively stable Proteus lac(+) strains. Proteus strains carrying F-linked lac(+) markers are heterogenotes and limited donors for lac(+). In addition, both the fertility and lac(+) property may be eliminated from Proteus by treatment with acridine orange. Escherichia and Proteus possess very different overall deoxyribonucleic acid (DNA) base compositions. In CsCl density gradients of DNA extracted from Proteus lac(+) strains, the acquisition of Escherichia genes by Proteus may be correlated with the addition of a physically recognizable high molecular weight, native DNA fraction of Escherichia base composition. Proteus lac(+) strains synthesize a beta-galactosidase which is indistinguishable from E. coli enzyme by several criteria. Despite this specificity, the regulatory functions of Escherichia lac(+) genes appear to be impaired in Proteus.
...
PMID:TRANSFER OF EPISOMIC ELEMENTS TO PROTEUS. I. TRANSFER OF F-LINKED CHROMOSOMAL DETERMINANTS. 1410 56


1 2 Next >>

---