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)

Calcium-induced aggregation has been proposed to play a role in the sorting and storage of secretory proteins in secretory granules of endocrine cells. The regulation of this process is not known. Hexahistidine epitope tags were used to create aggregation chaperones that enhance the calcium-induced aggregation of secretory granule proteins in vitro. Indeed, 100% recovery of the aggregating target protein was achieved without any modification of the target protein. The aggregation chaperone is not trapped in the aggregates. Co-expression of His(6)-tagged secreted alkaline phosphatase and the regulated secretory protein chromogranin A resulted in an increased chromogranin storage in secretory granules, and stimulated secretion of chromogranin A increased 50%. However, secretion of secreted alkaline phosphatase was not affected by the hexahistidine epitope tag. Thus, calcium-induced aggregation is not a passive process; rather, aggregation and sorting of secretory proteins can be regulated by aggregation chaperones in the secretory pathway of endocrine cells.
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PMID:Aggregation chaperones enhance aggregation and storage of secretory proteins in endocrine cells. 1086 58

The aim of this study was to evaluate the usefulness of a major secretory protein of human chondrocytes (chondrex) as a potential serum marker of bone responsiveness to growth hormone (GH). The study included 18 children (10 F, 8 M), aged 10.9 +/- 2.3 years, bone age 8.8 +/- 2.7 years, height -2.3 +/- 0.22 SDS, affected by isolated idiopathic GH deficiency (GHD). Serum samples for evaluation of chondrex, total, and bone alkaline phosphatase were taken before and 3 and 6 months following treatment with rhGH. The basal serum level of chondrex did not differ between patients (37 +/- 22 ng/ml) and controls (33 +/- 9.8 ng/ml). Following 6 months of treatment with rhGH, a significant increase of height velocity SDS (from -2.8 +/- 0.5 to 1.3 +/- 0.7), total (from 195 +/- 47 to 264 +/- 79 U/liter) and bone alkaline phosphatase (from 81 +/- 21 to 108 +/- 30 U/liter) was observed, while chondrex serum level remained unchanged (from 37 +/- 22 to 36 +/- 29 ng/ml). It was concluded that chondrex cannot be considered a reliable marker of bone responsiveness to GH in the growing child.
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PMID:Influence of growth hormone on a new marker of cartilage metabolism (chondrex). 1090 12

New secretion vectors containing the Bacillus sp. endoxylanase signal sequence were constructed for the secretory production of recombinant proteins in Escherichia coli. The E. coli alkaline phosphatase structural gene fused to the endoxylanase signal sequence was expressed from the trc promoter in various E. coli strains by induction with IPTG. Among those tested, E. coli HB101 showed the highest efficiency of secretion (up to 25.3% of total proteins). When cells were induced with 1 mM IPTG, most of the secreted alkaline phosphatase formed inclusion bodies in the periplasm. However, alkaline phosphatase could be produced as a soluble form without reduction of expression level by inducing with less (0.01 mM) IPTG, and greater than 90% of alkaline phosphatase could be recovered from the periplasm by the simple osmotic shock method. Fed-batch cultures were carried out to examine the possibility of secretory protein production at high cell density. Up to 5.2 g/l soluble alkaline phosphatase could be produced in the periplasm by the pH-stat fed-batch cultivation of E. coli HB101 harboring pTrcS1PhoA. These results demonstrate the possibility of efficient secretory production of recombinant proteins in E. coli by high cell density cultivation.
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PMID:Efficient secretory production of alkaline phosphatase by high cell density culture of recombinant Escherichia coli using the Bacillus sp. endoxylanase signal sequence. 1091 19

Previously we found that the carboxyl-terminal propeptide of type I collagen (c-propeptide) is a major secretory protein of MC3T3-E1 osteoblastic cells. In this study, we found that c-propeptide suppresses collagen synthesis and alkaline phosphatase activity of MC3T3-E1 osteoblastic cells at the early-differentiated stage in a dose dependent manner. Mature osteoblasts did not respond to c-propeptide. These findings imply that c-propeptide modulates the function of osteoblasts at an early differentiation stage. Transforming growth factor-beta (TGF-beta) is stored in bone and released from bone matrix after the resorption by osteoclasts. We investigated the effect of c-propeptide on the action of TGF-beta, and found that it enhanced the effect of TGF-beta. We conclude that c-propeptide is a physiological modulator of TGF-beta in bone metabolism.
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PMID:Carboxyl-terminal propeptide of type I collagen (c-propeptide) modulates the action of TGF-beta on MC3T3-E1 osteoblastic cells. 1098 19

Regulated secretory proteins are stored in secretory granules. While the sorting and storage process appears similar in endocrine and exocrine cells, the extent of overlap of sorting between endocrine and exocrine cell types is not clear. It is predicted that exocrine regulated secretory proteins that are stored with high efficiency in exocrine granules would also be stored efficiently in endocrine granules. To test this hypothesis, parotid secretory protein (PSP), which is stored efficiently in parotid acinar cells, was expressed in the endocrine cell lines GH4C1 and PC12. PSP undergoes stimulated secretion in both cell types. Secretion is similar to that of the endocrine regulated secretory protein chromogranin A but distinct from secreted alkaline phosphatase, a marker for the constitutive secretory pathway in endocrine cells. Subcellular fractionation of GH4C1 cells revealed that PSP co-fractionates with chromogranin A but not with secreted alkaline phosphatase.
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PMID:Sorting of an exocrine secretory protein to the regulated secretory pathway in endocrine cells. 1243 94

The constitutive and regulated secretory pathways represent the classical routes for secretion of proteins from neuroendocrine cells. Selective aggregation of secretory granule constituents in an acidic, bivalent cation-rich environment is considered to be a prerequisite for sorting to the regulated secretory pathway. The effect of selective vacuolar H+-ATPase (V-ATPase) inhibitor bafilomycin A1 on the pH gradient along the secretory pathway was used here to study the role of acidification on the trafficking of the regulated secretory protein chromogranin A (CgA) in PC12 cells. Sorting of CgA was assessed by three-dimensional deconvolution microscopy, subcellular fractionation, and secretagogue-stimulated release, examining a series of full-length or truncated domains of human CgA (CgA-(1-115), CgA-(233-439)) fused to either green fluorescent protein or to a novel form of secreted embryonic alkaline phosphatase (EAP). We show that a full-length CgA/EAP chimera is sorted to chromaffin granules for exocytosis. Inhibition of V-ATPase by bafilomycin A1 markedly reduced the secretagogue-stimulated release of CgA-EAP by perturbing sorting of the chimera (at the trans-Golgi network or immature secretory granule) rather than the late steps of exocytosis. The effect of bafilomycin A1 on CgA secretion depends on a sorting determinant located within the amino terminus (CgA-(1-115)) but not the C-terminal region of the granin. Moreover, examination of chromaffin granule abundance in PC12 cells exposed to bafilomycin A1 reveals a substantial decrease in the number of dense-core vesicles. We propose that a V-ATPase-mediated pH gradient in the secretory pathway is an important factor for the formation of dense-core granules by regulating the ability of CgA to form aggregates, a crucial step that may underlie the granulogenic function of the protein.
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PMID:Role of H+-ATPase-mediated acidification in sorting and release of the regulated secretory protein chromogranin A: evidence for a vesiculogenic function. 1554 60

Milk kappa-casein-derived glycomacropeptide has immunomodulatory and bacterial toxin binding effects. The intestinal anti-inflammatory activity of glycomacropeptide was assessed in trinitrobenzenesulfonic acid-induced colitis in rats. Rats were administered glycomacropeptide daily starting either 2 d before (pretreatment) or 3 h after (post-treatment) colitis induction. Pretreatment with glycomacropeptide had a dose-dependent anti-inflammatory effect, characterized by lower body weight loss, decreased anorexia (57%), colonic damage (65%), and weight to length ratio (32%), as well as a reduction in colonic alkaline phosphatase activity (42%) and interleukin 1, trefoil factor 3, and inducible nitric oxide synthase mRNA levels (P < 0.05). The mechanism of action of glycomacropeptide is unknown but is consistent with an inhibition of the activation of immune cells. The magnitude of the anti-inflammatory effect was generally comparable to that of sulfasalazine, an established drug used in the treatment of inflammatory bowel disease. Bovine glycomacropeptide may play a role in the management of patients with inflammatory bowel disease.
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PMID:Bovine glycomacropeptide is anti-inflammatory in rats with hapten-induced colitis. 1586 98

The advantages of using traceable fluorescent protein (enhanced green fluorescent protein; EGFP) and a secretory alkaline phosphatase (SEAP) have been used to generate a reporter gene: the secretory fluorescent protein (SEFP). Sf21 cells, infected with the recombinant baculovirus containing the SEFP gene, revealed both traceable fluorescence and easily detectable alkaline phosphatase activity in the culture medium. The distribution of SEFP within the cells revealed that it was excluded from the nucleus, implying that the accumulation of SEFP in a secretory pathway, similar to that of the secretion signal-tagged FPs. Furthermore, the time- and dose-dependent release from the blockage of brefeldin A (BFA) confirmed that the secretion of SEFP was mediated by the secretion pathway and excluded leakage from viral infection. This SEFP reporter gene with traceable fluorescence and alkaline phosphatase activity may become a useful tool for studies on secretory protein production.
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PMID:Secretory fluorescent protein, a secretion green fluorescent fusion protein with alkaline phosphatase activity as a sensitive and traceable reporter in baculovirus expression system. 1740 45

Active hexose correlated compound (AHCC) is a product prepared from the mycelium of edible Basidiomycete fungi that contains oligosaccharides. Here we have studied the antiinflammatory effect of AHCC in the trinitrobenzenesulfonic acid (TNBS) model of colitis in rats. Rats received AHCC (100 or 500 mg/kg) daily starting 2 d before (pretreatment) colitis induction and were killed 6 d after the TNBS challenge. The status of the rats was assessed by morphological and biochemical methods. The effect of AHCC on the colonic microflora was also assessed by studying the bacteria profile in feces by standard culture techniques. AHCC administration attenuated colonic inflammation, improving rat weight, food intake, damage score, extension of necrosis, colonic weight, colonic weight-to-length ratio, myeloperoxidase and alkaline phosphatase activities, glutathione concentration, and the expression of proinflammatory cytokines and chemokines (IL-1beta, IL-1 receptor antagonist, TNF, and monocyte chemoattractant protein-1) and of mucins 2-4 and trefoil factor 3. The magnitude of the antiinflammatory effect of AHCC was similar to that of sulfasalazine (200 mg/kg). The study of colonic microflora indicated that rats treated with AHCC had higher aerobic and lactic acid bacteria counts as well as higher bifidobacteria counts, whereas clostridia were reduced when compared with the TNBS group. Therefore, our results indicate that AHCC is antiinflammatory and could be useful as a prebiotic to design functional foods for inflammatory bowel disease patients.
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PMID:Active hexose correlated compound acts as a prebiotic and is antiinflammatory in rats with hapten-induced colitis. 1744 85

Efficient export of secretory alkaline phosphatase (ALP) from the endoplasmic reticulum depends on the conserved transmembrane sorting adaptor Erv26p/Svp26p. In the present study we investigated the mechanism by which Erv26p couples pro-ALP to the coat protein complex II (COPII) export machinery. Site-specific mutations were introduced into Erv26p, and mutant proteins were assessed in cell-free assays that monitor interactions with pro-ALP cargo and packaging into COPII vesicles. Mutations in the second and third loop domains of Erv26p inhibited interaction with pro-ALP, whereas mutations in the C-terminal tail sequence influenced incorporation into COPII vesicles and subcellular distribution. Interestingly mutations in the second loop domain also influenced Erv26p homodimer associations. Finally we demonstrated that Ktr3p, a cis-Golgi-localized mannosyltransferase, also relies on Erv26p for efficient COPII-dependent export from the endoplasmic reticulum. These findings demonstrate that Erv26p acts as a protein sorting adaptor for a variety of Type II transmembrane cargo proteins and requires domain-specific interactions with both cargo and coat subunits to promote efficient secretory protein transport.
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PMID:Molecular dissection of Erv26p identifies separable cargo binding and coat protein sorting activities. 1957 29


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