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)

Enzymes considered to be markers for neurons (angiotensin converting enzyme, thermolysin-like metalloendopeptidase, alanine aminopeptidase, and glutamate-oxaloacetate transaminase), glia (glutamine synthetase, pyruvate carboxylase, and beta-glucuronidase), and endothelial cells (alkaline phosphatase and plasminogen activator) were measured in caudate nucleus from 10 sudden death controls, eight agonal state controls, and 16 Huntington's disease patients. Glutamate-oxaloacetate transaminase was slightly reduced by agonal state. The four enzymes with a neuronal distribution were all correlatively reduced in Huntington's disease caudate nucleus. Glutamine synthetase activity was reduced and beta-glucuronidase mean activity increased over twofold in Huntington's disease caudate nucleus, with the two enzyme activities being inversely related. Pyruvate carboxylase was markedly affected by agonal state and was very variable in Huntington's disease caudate nucleus. The two endothelial enzymes were unaltered in Huntington's disease caudate nucleus. The findings are indicative of neuronal loss, an increased proportion of altered glia, and also of maintained vasculature in Huntington's disease caudate nucleus. Measurement of enzyme activities can help to delineate the types of cell altered in Huntington's disease.
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PMID:Changes in nine enzyme markers for neurons, glia, and endothelial cells in agonal state and Huntington's disease caudate nucleus. 287 90

At present it is not clear whether N-methyl-D-aspartate and N-methyl-D-aspartate receptor agonists have a direct excitotoxic effect on somatostatin interneurons in rat striatum. The N-methyl-D-aspartate receptor comprises a multivariant complex encoded by a family of subunit complementary DNAs. Evidence suggests that expression of the N-methyl-D-aspartate receptor subunit NR1 (zeta 1) is essential for functional receptors. To investigate the expression of NR1 messenger RNA by striatal somatostatin cells, a dual in situ hybridization technique was applied to fresh frozen tissue sections. Cellular sites of NR1 and somatostatin gene expression were visualized in the same tissue section using [35S]NR1 and alkaline phosphatase-labelled somatostatin oligonucleotides. Only 8-18% of striatal somatostatin cells expressed a strong NR1 hybridization signal; most cells (> 80%) expressed a weak or undetectable signal. In contrast NR1 messenger RNA was enriched in neighbouring medium-sized non-somatostatin cells. These data suggest that while the NR1 gene is expressed in some striatal somatostatin cells most do not express a strong NR1 signal, a finding which may explain, in part, the preferential survival of somatostatin cells in Huntington's disease.
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PMID:Expression of N-methyl-D-aspartate receptor subunit NR1 messenger RNA by identified striatal somatostatin cells. 791 Jun 73

The Unocal-Metrolink oil spill of 21 February 1995 resulted in approximately 7800 barrels of San Joaquin crude oil being deposited into the San Gabriel River in Huntington Beach, CA, USA. In order to determine long-term pathological effects of oil exposure and rehabilitation, hematological and serum biochemical parameters for both rehabilitated (RHB) American coots (Fulica americana) and reference (REF) coots were examined every 3-4 weeks (56, 81, 108 and 140 days post oil exposure) after birds were cleaned, rehabilitated and soft-released. Most significant differences in monthly comparisons between RHB and REF birds occurred 56 days following oil exposure. Total white blood cell (WBC) count, albumin:globulin (A:G) ratio and calcium concentration were higher in RHB birds compared to REF birds 56 days post oil exposure. In addition, mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and creatine kinase activities, and creatinine, total protein (TP) and globulin concentrations were lower in RHB birds. Blood results from 56 days post oil exposure for RHB coots which subsequently died were compared to blood results from days 108 and 140 for REF coots which survived. Oiled and rehabilitated birds which died had significantly higher WBCs, packed cell volume, TP and globulin concentrations, and lower A:G ratio, MCH, MCHC, glucose and sodium concentrations compared to REF birds which survived. Blood result differences detected at 3-4-week intervals between RHB and REF survivors, and differences detected between RHB coots which died and REF coots which survived, suggested that RHB coots developed an inflammatory response (infectious or non-septic) and, concurrently, may have experienced decreased immune responsiveness. Additionally, RHB coots experienced either an iron (Fe) utilization or Fe metabolism problem. These pathophysiological mechanisms were consistent with increased hemosiderin (stored Fe) present in the liver, spleen and kidney of necropsied RHB birds, and may have contributed to RHB coot mortality. When blood parameter differences were examined for their impact on survival time, it was determined that RHB coots had shorter survival times if they had very high cholesterol (> or =449 mg/dl) or chloride (> or =110 MEQ/l) concentrations on day 56 post oil exposure. Interestingly, the lack of differences between RHB and REF coots from day 81 through day 140 suggested that, from a hematologic and clinical chemistry perspective, coots which were oiled, rehabilitated, released and survived at least 3.5 months could not be differentiated from wild (REF) coots. From these findings it appears that blood analysis, coupled with post-release survival data, may help discern reasons for increased mortality of oiled and rehabilitated birds, compared to non-oiled reference birds.
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PMID:An experimental soft-release of oil-spill rehabilitated American coots (Fulica americana): II. Effects on health and blood parameters. 1509 75

Huntingtin (Htt) is a large protein of 3144 amino acids, whose function and regulation have not been well defined. Polyglutamine (polyQ) expansion in the N terminus of Htt causes the neurodegenerative disorder Huntington disease (HD). The cytotoxicity of mutant Htt is modulated by proteolytic cleavage with caspases and calpains generating N-terminal polyQ-containing fragments. We hypothesized that phosphorylation of Htt may modulate cleavage and cytotoxicity. In the present study, we have mapped the major phosphorylation sites of Htt using cell culture models (293T and PC12 cells) expressing full-length myc-tagged Htt constructs containing 23Q or 148Q repeats. Purified myc-tagged Htt was subjected to mass spectrometric analysis including matrix-assisted laser desorption/ionization mass spectrometry and nano-HPLC tandem mass spectrometry, used in conjunction with on-target alkaline phosphatase and protease digestions. We have identified more than six novel serine phosphorylation sites within Htt, one of which lies in the proteolytic susceptibility domain. Three of the sites have the consensus sequence for ERK1 phosphorylation, and addition of ERK1 inhibitor blocks phosphorylation at those sites. Other observed phosphorylation sites are possibly substrates for CDK5/CDC2 kinases. Mutation of amino acid Ser-536, which is located in the proteolytic susceptibility domain, to aspartic acid, inhibited calpain cleavage and reduced mutant Htt toxicity. The results presented here represent the first detailed mapping of the phosphorylation sites in full-length Htt. Dissection of phosphorylation modifications in Htt may provide clues to Huntington disease pathogenesis and targets for therapeutic development.
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PMID:Huntingtin phosphorylation sites mapped by mass spectrometry. Modulation of cleavage and toxicity. 1678 7

Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- and cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity indicated by the Unified Huntington's disease rating scale-Total Functional Capacity Score (UHDRS-TFC). For gamma-glutamyl transferase, elevated levels were more frequent in the manifest groups than in both the HD gene-expansion negative controls and premanifest HD gene-expansion carriers. Finally, the manifest HD gene-expansion carriers displayed moderate increases in total cholesterol and blood glucose relative to the premanifest HD gene-expansion carriers, as well as increased C-reactive protein relative to HD gene-expansion negative controls. Our results show that LFT values are elevated more frequently in manifest compared to premanifest HD gene-expansion carriers and controls. The majority of the manifest HD gene-expansion carriers receive medication, and it is possible that this can influence the liver function tests performed in this study.
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PMID:Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting. 2694 72

The Genea020 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 48 repeats, indicative of Huntington disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 89% of cells expressed Nanog, 95% Oct4, 29% Tra1-60 and 99% SSEA4, gave a Pluritest pluripotency score of 27.51, novelty of 1.43 and demonstrated alkaline phosphatase activity. The cell line was negative for Mycoplasma and visible contamination.
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PMID:Derivation of Huntington disease affected Genea020 human embryonic stem cell line. 2734 7

The Genea017 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, genetic analysis confirmed a 46, XY karyotype and male allele pattern through CGH and STR analysis. The hESC line had pluripotent cell morphology, 87% of cells expressed Nanog, 95% Oct4, 88% Tra1-60 and 99% SSEA4, gave a PluriTest pluripotency score of 34.74, novelty of 1.27, demonstrated alkaline phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination.
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PMID:Derivation of Huntington Disease affected Genea017 human embryonic stem cell line. 2734 22