Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

VH (heavy-chain variable region) and VL (light-chain variable region) genes were amplified by PCR from hybridomas producing MAb-11 and MAb-18 which inhibited Japanese radish acid phosphatase. Nucleotide sequencing of the V genes demonstrates that the MAbs contained similar VH and identical VL domains. Initially, the VH and VL genes were expressed in Escherichia coli as single-chain Fv (ScFv) fragments. Fragments ScFv-11 and ScFv-18, named for MAb-11 and MAb-18, respectively, inhibited the enzyme activity to the same extent as the intact MAbs. Both of the antibody fragments widely cross-reacted with other phosphatases, including some phosphomonoesterases and phosphodiesterases from different sources. ScFv-18 also inhibited acid phosphatase from a different origin, but stimulated the activity of alkaline phosphatase from calf intestine. The PCR-amplified VH and VL genes were subsequently expressed separately in Escherichia coli as fusion products with glutathione S-transferase. The fusion proteins had little effect on Japanese radish acid phosphatase. Furthermore, a large number of recombinant ScFv fragments specific to the acid phosphatase were generated by using a bacteriophage expression system and a mouse ScFv gene library. These ScFv fragments had a range of effects on the enzyme activity, including inhibition, stimulation, and none. Among them, an ScFv fragment, designated ScFv-G7, inhibited more strongly than ScFv-11 and ScFv-18.
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PMID:Antibody fragments as inhibitors of Japanese radish acid phosphatase. 969 84

The systemic and neurobehavioral effects of benzo[b]thiophene (routinely referred to as benzothiophene) were studied in rats following 13-wk oral exposure. Male (170 +/- 16 g) and female (146 +/- 12 g) Sprague-Dawley rats (10 animals per group) were fed diet containing 0.5, 5, 50, or 500 ppm benzothiophene for 13 wk. Control animals were given rat feed plus vehicle (corn oil) only. No clinical signs of toxicity and neurobehavioral effects were observed using screening tests that included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. Elevated serum aspartate aminotransferase activity and bilirubin level were observed in highest dose females. Except for a statistically significant decrease in hematocrit in the highest dose males, benzothiophene exerted no marked effects on hematological parameters. Benzothiophene exposure did not result in alterations in hepatic alkaline phosphatase activity, or the typical hepatic phase I (aniline hydroxylase, ethoxyresorufin O-deethylase, pentoxyresorufin O-dealkylase, aminopyrine N-demethylase) and phase II (UDP-glucuronosyltransferase, glutathione S-transferase) drug-metabolizing enzyme activities. No significant elevation in urinary ascorbic acid, protein, and N-acetylglucosaminidase activity was detected in the treated animals. Peribiliary fibrosis was the most significant histological change and occurred in the liver of females in the 50 and 500 ppm groups. Mild epithelial hyperplasia in the renal pelvis was detected in the majority of 5 and 50 ppm females, with epithelial hyperplasia in the urinary bladder observed in the 50 ppm females. In males, increased incidence and severity of mild binucleation of hepatocytes and mild thickening of the basement membrane in kidney cortex were observed at 500 ppm. Benzothiophene was not detected in the urine of high-dose animals at the termination of the experiment. Based on the kidney, hepatic, and hematocrit changes, the no-observed-adverse-effect level (NOAEL) in the diet was determined to be 0.5 ppm (0.04 mg/kg/d) for females and 50 ppm (3.51 mg/kg/d) for males.
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PMID:Subchronic toxicity of benzothiophene on rats following dietary exposure. 976 Nov 33

The effects of vitamin C and aloe vera gel extract supplementation on induced hepatocarcinogenesis in male Sprague-Dawley rats (120-150 g) by diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) was investigated. The severity of the carcinogenesis process was determined by measuring gamma-glutamyl transpeptidase (GGT) and the placental form of glutathione S-transferase (GSTP) histochemically in situ and in plasma and liver fractions. In addition, plasma alkaline phosphatase (ALP) and liver microsomal uridine diphosphate glucuronyl transferase (UDPGT) activity were also determined. Administration of DEN/AAF caused an increase in the surface area and number of enzyme-positive foci (both GGT and GSTP) compared with control. Supplementation of vitamin C or aloe vera gel extract to the cancer-induced rats suppressed this increase significantly (P < 0.05; P < 0.001). Increases in liver UDPGT, GGT, and GSTP activities were also observed with cancer induction that were again suppressed with either vitamin C or aloe vera gel supplementation. Plasma GGT in the DEN/AAF rats were determined monthly for the duration of the experiment and found to be reduced as early as 1 mo with aloe vera gel supplementation and 2 mo with vitamin C supplementation. In conclusion, vitamin C and aloe vera gel extract supplementation were found to be able to reduce the severity of chemical hepatocarcinogenesis.
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PMID:Vitamin C and aloe vera supplementation protects from chemical hepatocarcinogenesis in the rat. 983 27

Extracts of Emblica officinalis (EO), Phyllanthus amarus (P. amarus) and Picrorrhiza kurroa (P. kurroa) significantly inhibited hepatocarcinogenesis induced by N-nitrosodiethylamine (NDEA) in a dose dependent manner. The anticarcinogenic activity of these extracts were evaluated by their effect on tumour incidence, levels of carcinogen metabolizing enzymes, levels of liver cancer markers and liver injury markers. Animals treated with NDEA alone showed 100% tumour incidence and significantly elevated tissue levels of drug metabolizing enzymes such as glutathione S-transferase (GST) and aniline hydroxylase (AH). Treatment of extracts significantly reduced these levels. Levels of gamma-glutamyl transpeptidase (GGT) were also found to be elevated both in serum and tissues of tumour bearing animals, while they were significantly reduced in the treated group. Similar reduction was seen in tissue levels of reduced glutathione. Serum levels of lipid peroxide (LPO), alkaline phosphatase (ALP) and glutamate pyruvate transaminase (OPT), which are markers of liver injury, were also elevated. Morphology of liver tissue and levels of marker enzymes indicated that these extracts offered protection against chemical carcinogenesis.
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PMID:Effect of Emblica officinalis, Phyllanthus amarus and Picrorrhiza kurroa on N-nitrosodiethylamine induced hepatocarcinogenesis. 1021 33

Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis was highly purified from the thermophilic bacterium Thermus thermophilus. The enzyme preparation showed a single band on SDS-polyacrylamide gel electrophoresis, a pH optimum of 7.5 and a temperature optimum at 60 degrees C. The native enzyme which is phosphorylated could, upon treatment with alkaline phosphatase, lose all activity. The inactive form could be reversibly activated by nucleotides in the order of NTP>NDP>NMP. When physiological polyamines were added to the purified enzyme in vitro, spermine or spermidine activated ODC by 140 or 40%, respectively, while putrescine caused a small inhibition. The basic amino acids lysine and arginine were competitive inhibitors of ODC, while histidine did not affect the enzyme activity. Among the phosphoamino acids tested, phosphoserine was the most effective activator of purified ODC. Polyamines added at high concentration to the medium resulted in a delay or in a complete inhibition of the growth of T. thermophilus, and in a decrease of the specific activity of ornithine decarboxylase. The decrease of ODC activity resulted from the appearance of a non-competitive inhibitor of ODC, the antizyme (Az). The T. thermophilus antizyme was purified by an ODC-Sepharose affinity column chromatography, as well as by immunoprecipitation using antibodies raised against the E. coli antizyme. The antizyme of E. coli inhibited the ODC of T. thermophilus, and vice versa. The fragment of amino acids 56-292 of the E. coli antizyme, produced as a fusion protein of glutathione S-transferase, did not inhibit the ODC of E. coli or T. thermophilus.
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PMID:Characterization of ornithine decarboxylase and regulation by its antizyme in Thermus thermophilus. 1039 69

(5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5- methoxymethyl-2-oxazolidinone (E2011) is a novel monoamine oxidase type-A (MAO-A) inhibitor. In order to assess toxicological profiles of E2011, doses of 0 (as controls), 30, 100 mg/kg of E2011 were administered to male and female Sprague-Dawley rats once a day for 13 weeks orally by gavage. No mortality or any toxic signs except salivation occurred due to E2011 treatment. Decreased body weight gain and food consumption, increases of alkaline phosphatase and increases of liver weight were the major treatment-related findings observed predominantly in the 100 mg/kg group. Histological examination revealed nuclear enlargement of hepatocytes with appearance of altered cell foci in some cases, and acinar atrophy in Harderian glands in the 100 mg/kg group. Since the histopathological findings in the liver were indicative of an ongoing carcinogenic process, glutathione S-transferase placental form (GST-P) positive hepatic foci were identified immunohistochemically and examined morphometrically. Although GST-P positive hepatic foci were detected in all groups including controls, the number and area of GST-P positive hepatic foci were significantly higher in female rats treated with 100 mg/kg than those in controls. In this paper, possible mechanisms of specific lesions in the liver and Harderian glands will be discussed.
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PMID:Toxicological response of rats to a novel monoamine oxidase type-A inhibitor, (5R)-3-[2-((1S)-3-cyano-1-hydroxypropyl)benzothiazol-6-yl]-5- methoxymethyl-2-oxazolidinone (E2011), orally administered for 13 weeks. 1047 31

The developmental profile of certain enzymatic antioxidants as well as the generation of reactive oxygen species was studied in the rat cerebral microvessels during first three weeks of life and the levels were compared to those present in adults. The data showed a higher generation of superoxide anion (+67%) and H2O2 (+200%) at postnatal day (PND) 21. Superoxide anion production was significantly lower (-24%) at PND 14 and almost comparable to adult values at PND 7. The activity of superoxide dismutase increased with development and attained an adult level at PND 21. Catalase was higher in neonates with a maximum activity at PND 7 and 14 (+68, 69%). The measurement of microvessel glutathione and glutathione-related antioxidant enzymes showed that glutathione level was higher at PND 7, which declined to an adult level at PND 14. Se-dependent GPx showed a marked increase between PND 14 and 21, however, it declined in adults. The activity of Se-independent glutathione peroxidase was very low in cerebral microvessels. Glutathione reductase activity in 7-day-old, that was comparable to adult level, declined at PND 14 and 21. The level of glutathione S-transferase was higher (+43%) at PND 21. The activity of microvessel marker enzyme gamma-glutatmyl transpeptidase increased with age, whereas, alkaline phosphatase showed a slight increase up to PND 14 and thereafter it declined. Lipid peroxidation was found to be significantly lower (-18%) at PND 21 as compared to adults. It may be concluded that developing cerebral microvessels contain high levels of several antioxidant enzymes that are more or equal to those present in adult brain microvessels.
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PMID:Developmental pattern of reactive oxygen species generation and antioxidative defense machinery in rat cerebral microvessels. 1056 84

Although gum kondagogu (Cochlospermum gossypium) is grouped under gum karaya (Sterculia sp.), it differs significantly in terms of physicochemical properties and chemical composition and does not conform to the confirmatory tests prescribed for gum karaya ([Janaki]). Gum karaya has wide applications in the pharmaceutical and food industries, whereas the use of gum kondagogu is yet to be explored. In this context, a short-term toxicity study on gum kondagogu was undertaken in rats. The gum was fed to rats at 0, 0.2%, 1% and 5% (w/w) in feed, for 90 days. Biochemical parameters were measured to assess the toxicity at the end of the study period. The results indicated no significant changes in growth pattern, haematological indices (RBC, WBC, Hb, PCV, MCV, MCH, MCHC, differential leucocyte counts), biochemical analytes (glucose, urea nitrogen, total protein, albumin, bilirubin, creatinine, sodium and potassium ions), activities of plasma and liver enzymes (alkaline phosphatase, alanine amino-transaminase, aspartate aminotransaminase, lactate dehydrogenase, glutathione S-transferase and gamma-glutamyl transpeptidases and organ to body mass ratio (brain, heart, lungs, liver, kidneys and spleen). Histopathology of the liver and kidney also did not reveal any abnormality. An increased faecal bulk was observed in rats fed with 5% gum kondagogu. However, faecal moisture content of female rats only was significantly different (P=<0.05) as compared to controls. Thus, it can be inferred, based on the present investigations, that gum kondagogu has a potential application as a food additive, similar to gum karaya. Feeding it at a much higher level (5%) than expected for consumption as a food additive also did not result in any toxic effect. Being non-toxic, gum kondagogu has a potential as a food additive with excellent physicochemical properties and a unique chemical composition.
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PMID:Subchronic (90-day) toxicity study in rats fed gum kondagogu (Cochlospermumgossypium). 1082 4

The effect of Phyllanthus amarus extract administration after induction of hepatocellular carcinoma (HCC) by N-nitrosodiethylamine (NDEA) was studied in Wistar rats. Administration of an aqueous extract of P. amarus was found to significantly increase the survival of hepatocellular carcinoma harboring animals. All the untreated rats died of tumour burden by 33.7+/-1.6 weeks. Administration of P. amarus extract (150 mg/kg b.w.) after tumour development increased the survival of animals to an average of 52. 2+/-2.3 weeks. Serum gamma-glutamyl transpeptidase activity which was elevated to 182+/-23 U/l by NDEA administration was lowered to 112+/-19 U/l by the administration of P. amarus extract. Similarly elevated glutathione S-transferase activity (1534+/-116 nmol/min per mg protein) and glutathione (20.5+/-2.4 nmol/mg protein) levels in the NDEA administered group were found to be lowered to 1112+/-89 nmol/min per mg protein and 14.2+/-2.2 nmol/mg protein respectively. P. amarus administration was found to be ineffective in controlling the liver weight, elevation of tissue gamma-glutamyl transpeptidase, serum alkaline phosphatase and serum glutamate pyruvate transaminase of HCC harboring animals.
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PMID:Phyllanthus amarus extract administration increases the life span of rats with hepatocellular carcinoma. 1102 59

Evolutionary information derived from the large number of available protein sequences and structures could powerfully guide both analysis and prediction of protein-protein interfaces. To test the relevance of this information, we assess the conservation of residues at protein-protein interfaces compared with other residues on the protein surface. Six homodimer families are analyzed: alkaline phosphatase, enolase, glutathione S-transferase, copper-zinc superoxide dismutase, Streptomyces subtilisin inhibitor, and triose phosphate isomerase. For each family, random simulation is used to calculate the probability (P value) that the level of conservation observed at the interface occurred by chance. The results show that interface conservation is higher than expected by chance and usually statistically significant at the 5% level or better. The effect on the P values of using different definitions of the interface and of excluding active site residues is discussed.
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PMID:Protein-protein interfaces: analysis of amino acid conservation in homodimers. 1109 65


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