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

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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)

We produced an immortalized colonic epithelial cell line, MCE301, using fetal mice transgenic for the temperature-sensitive simian virus 40 large T-antigen gene. MCE301 cells showed epithelial-like morphology and maintained tight connections with neighboring cells. The cells grew at a permissive temperature (33 degrees C), but the growth of the cells was significantly prevented at the nonpermissive temperature (39 degrees C). The cells expressed large T-antigen at 33 degrees C but not at 39 degrees C. MCE301 cells were not transformed, as judged by the absence of anchorage-independent growth in soft agar gel and lack of tumor formation in nude mice. Electron microscopic studies showed that the cells formed microvilli-like structures on the cell surface and junctional complexes such as tight junctions and desmosomes between the cells. The cells expressed cytosketal (acidic cytokeratins and actin), basement membrane (laminin and collagen type IV) and junctional complex proteins (ZO-1 and desmoplakin I + II), as judged by specific antibodies. Fetal bovine serum, epidermal growth factor, insulin-like growth factor and insulin significantly increased the cell growth at 33 degrees C. Moreover, MCE301 cells expressed colonic mucin Muc2 mRNA as demonstrated by reverse transcriptase-polymerase chain reaction, indicating that the cells originate from mucus-secreting cells. Alkaline phosphatase, a brush border-associated enzyme, was detected in the cells. Sodium butyrate (2 mM), an inducer of cellular differentiation, markedly elevated alkaline phosphatase activity. Thus, the present mouse colonic epithelial cell line MCE301 possessing these unique characteristics should provide a useful in vitro model of colonic epithelium.
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PMID:Establishment and characterization of a colonic epithelial cell line MCE301 from transgenic mice harboring temperature-sensitive simian virus 40 large T-antigen gene. 1123 98

Renal osteodystrophy is a metabolic bone disease occurring in patients with end-stage renal failure. The aim of the study was to compare serum concentrations of some bone markers in hemodialysed (HD) patients and in patients undergoing continuous ambulatory peritoneal dialysis (CADO). We studied two groups of patients with end-stage renal failure: 52 hemodialysed individuals aged 24-74 years and 19 peritoneally dialysed patients aged 20-70 years. Serum calcium and phosphate concentration, cholesterol, triglycerides, total protein, albumin, alkaline phosphatase, urea before and after HD, urea in CADO patients were determined by standard laboratory methods. Serum PTH, osteocalcin, 1,25(OH)2D3 and insulin-like growth factor (IGF-1) concentrations were measured by commercially available radioimmunoassay. Serum tumor necrosis factor (TNF-alpha) and interleukin-1 (IL-1) concentrations were measured by ELISA. There were no differences between serum concentrations of the studied bone markers in hemodialysed patients and CAPD patients. All dialysed patients presented high concentrations of serum PTH, osteocalcin, alkaline phosphatase activity, lower serum IGF-1 concentration and normal serum calcitriol concentration. High serum PTH and osteocalcin concentrations may indicate intensification of bone synthesis, what is typical for osteitis fibrosa.
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PMID:[Selected parameters of bone metabolism in hemodialyzed and peritoneally dialyzed patients]. 1139 92

Pycnodysostosis is a rare hereditary bone abnormality with an autosomal recessive mode of inheritance. We report the clinical, radiologic, and endocrine status of 8 children with this rare disease. All patients had the characteristic phenotype of the disorder including short stature (8 of 8), increased bone density (7 of 8), separated cranial sutures (8 of 8), large fontanel with delayed closure (8 of 8), obtuse mandibular angle (8 of 8), delayed teeth eruption (8 of 8), enamel hypoplasia (7 of 8), dysplastic acromial ends of the clavicles (6 of 8), frontal bossing (6 of 8), ocular proptosis (8 of 8), and dysplastic nails (8 of 8). Developmental evaluation according to the revised Denever developmental screening showed normal motor, fine motor-adaptive language, and personal social abilities in all the children. All had normal hepatic and renal functions. Serum calcium and phosphorus concentrations were normal. Two children had low serum alkaline phosphatase concentration. Short stature is a characteristic feature of pycnodysostosis. Seven of the 8 children were born short (length standard deviation score [SDS] = -3 to -1.5). Deceleration of linear growth was significant during the first 3 years of life. All the children had height SDS below -3 at the end of their third year of life. Although short stature is a feature of this genetic disorder, defective growth hormone (GH) secretion in response to provocation with clonidine and glucagon was found in 4 of the 8 patients. These 4 patients had pituitary hypoplasia on the magnetic resonance imaging (MRI) of their brain. In addition, 3 of these 4 patients had demyelination of the cerebrum. Patients with pycnodysostosis (n = 8) had low circulating concentrations of insulin-like growth factor-1 (IGF-1) compared with normal age-matched short children with constitutional short stature (CSS). IGF-I increased significantly after injecting GH for 3 days in these patients. Physiologic replacement with GH (18 U/m(2)/week) divided in daily evening doses subcutaneously increased IGF-1 concentration and improved linear growth velocity and height standard deviation scores (HtSDS) in the 4 children with GH deficiency. These data ruled out GH resistance and proved the usefulness of GH therapy in the management of short stature in these patients. In summary, some patients with pycnodysostosis have partial GH deficiency and low IGF-1 concentration. GH therapy markedly increases IGF-I secretion and improves their linear growth. MRI study of the brain including the hypothalamic-pituitary area is recommended in these children because of the high incidence of pituitary hypoplasia and cerebral demyelination.
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PMID:Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy. 1147 77

The present studies were designed to determine whether recombinant human growth hormone (rhGH) can counteract some of the catabolic effects of glucocorticosteroid therapy in children chronically treated with glucocorticosteroids. Whether rhGH can safely improve short-term linear growth was also investigated. The effect of rhGH on disease activity was also assessed. Ten children (6 boys, 4 girls) with inflammatory bowel disease (IBD) on oral prednisone for at least 4 months prior to these studies were recruited (mean +/- SE, 11.9 +/- 0.9 years). Leucine and glucose isotope studies, body composition, substrate oxidation and energy expenditure rates, and growth factors were measured at baseline (D1) and at 4 months after treatment with rhGH (0.05 mg/ kg. d subcutaneously [SC]) while continuing oral prednisone. Dual-emission x-ray absorptiometry (DEXA) and calcium kinetic analysis ((42)Ca/(46)Ca) were performed also. rhGH was continued for 6 months to assess linear growth in all 10 subjects, 7 of whom continued rhGH for 12 months. Body composition changed favorably with increased fat free mass (+3 kg, P =.001) and decreased percent fat mass (-3.5%, P =.001) after 4 months of treatment. Rates of whole body protein turnover, oxidation, and synthesis remained invariant, with no changes in substrate oxidation or resting energy expenditure rates. Linear growth velocity increased from 3.5 +/- 0.4 cm/yr when the patients were treated with prednisone only, to 7.7 +/- 0.9 after 6 months of combined prednisone/rhGH (P =.001). The growth velocity was sustained in the 7 patients treated with rhGH for 12 months. Plasma insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations also increased significantly while on rhGH treatment. No changes in calcium absorption were observed but there was a significant increase in kinetic rates of bone calcium accretion (P =.045) as well as in bone-specific alkaline phosphatase concentrations, a measure of bone formation (P =.03). Fasting and 2-hour postprandial glucose concentrations, fasting insulin levels, and HbA(1C) were invariant during combined rhGH/prednisone treatment. The Crohn's disease activity score was unchanged with rhGH therapy. In summary, rhGH treatment of corticosteroid-dependent patients with IBD was associated with positive changes in body composition, bone metabolism, and linear growth, without deterioration of carbohydrate tolerance or intermediate metabolism of substrates. We conclude that treatment with rhGH has beneficial effects in prednisone-dependent growing children. Larger studies will be needed to assess the long-term safety and efficacy of this approach.
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PMID:Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a pilot study. 1178 84

The aim of this study was to investigate the effects of tibolone in the prevention of postmenopausal bone loss over 3 years, and to compare these with the effects of sequential hormone replacement therapy. Forty early postmenopausal women were randomized to a 21-day regimen of conjugated equine estrogens (CEE, Premarin) plus sequential medroxyprogesterone acetate (MPA, Prodafem), or tibolone (Livial) daily. In total, 36 women completed 12 months and were considered for the intent-to-treat analysis, 34 completed 24 months and 23 completed 36 months. Main drop-out reasons were: lost to follow-up (n = 9) and minor side-effects (n = 4). Bone mineral density was measured at baseline and after 6, 12, 24 and 36 months, using dual-energy X-ray absorptiometry at the lumbar spine and the upper femur (neck, trochanter, total hip). In both groups, bone loss was prevented. Treatment with tibolone demonstrated significant increases in bone density at the spine (+4.6%; p < 0.01), at the total hip (+3.2%; p < 0.01) and at the trochanter (+4.5%; p < 0.01), whereas the CEE/MPA group showed a non-significant increase of bone mineral density at the lumbar spine (+2.6%) but no increases at the hip. Between-group differences in bone mineral density changes were significant (p < 0.05) for the total hip and the trochanter at 36 months. This increase of bone mineral density was not accompanied by changes in insulin-like growth factor-I (IGF-I) or insulin-like growth factor binding protein-3 (IGFBP-3) in either group. Osteocalcin, alkaline phosphatase and urinary ratios of hydroxyproline/creatinine and calcium/creatinine significantly decreased in both groups. In conclusion, sequential CEE/MPA prevented cortical and trabecular bone loss, with a transient increase of bone mineral density only during the first 6 months. Tibolone not only prevented cortical and trabecular bone loss, but further increased bone mineral density at the lumbar spine and at the hip throughout the 3 years of treatment, suggesting a sustained positive effect on bone mass.
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PMID:A 3-year study of prevention of postmenopausal bone loss: conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone. 1190 45

All-trans -retinoic acid (atRA) inhibits osteoblast marker gene expression and markedly increases expression of insulin-like growth factor binding protein-6 (IGFBP-6) in human osteoblasts. The possibility that IGFBP-6 inhibits the osteoblast phenotype and also mediates the inhibitory effect of atRA on osteoblast marker gene expression was explored using an antisense approach. Stable human osteoblast-like osteosarcoma SaOS-2 cells were prepared that expressed antisense IGFBP-6 RNA under basal and atRA-stimulated conditions. The functional expression of IGFBP-6 antisense RNA was confirmed by measuring IGFBP-6 mRNA by Northern analysis or by measuring IGFBP-6 protein in the conditioned media (CM) by radioimmunoassay. Antisense clones produced less mRNA and had less IGFBP-6 protein in the CM than controls. IGFBP-6 protein levels in the CM were inversely correlated with alkaline phosphatase (ALP) activity, whereas IGFBP-3 and IGFBP-4 protein levels were not. We reasoned that atRA would have little or no effect on ALP activity in IGFBP-6 antisense clones if atRA mediated its inhibitory effects by recruiting IGFBP-6. In the majority of IGFBP-6 antisense clones with the lowest IGFBP-6 mRNA and CM protein levels and only modest changes in other IGF system components, atRA did not significantly decrease ALP activity. These findings provide evidence that atRA recruits IGFBP-6 to inhibit the human osteoblast phenotype.
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PMID:Inhibition of human osteoblast marker gene expression by retinoids is mediated in part by insulin-like growth factor binding protein-6. 1191 24

The effects of melatonin on osteoclastic and osteoblastic cells were examined using a culture system of the goldfish scale. Tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP) were used as markers of osteoclastic and osteoblastic cells, respectively. In Earle's minimum essential medium containing melatonin (10(-9) to 10(-5) m), activities of both enzymes in scales were significantly suppressed at 6 hr after incubation (TRACP: 10(-8), 10(-6), 10(-5) m; ALP: 10(-7) to 10(-5) m), but at 18 hr only ALP activity was significantly lowered (10(-8), 10(-7) m). Estradiol-17beta (E(2)) enhanced both activities, which were significantly inhibited and brought down to the level of the controls when co-incubated with E(2) and melatonin (TRACP at 6 hr: 10(-9) to 10(-5) m; ALP at 6 hr: 10(-7) m; ALP at 18 hr: 10(-8) m). Moreover, using reverse-transcription polymerase chain reaction, the mRNA expression of the estrogen receptor (ER) and insulin-like growth factor (IGF)-1, which are related to osteoblastic growth and differentiation, was decreased in the melatonin-treated scales. These results suggest that melatonin acts directly on the scale osteoclastic and osteoblastic cells where it suppresses the ALP activity via down-regulation of ER and IGF-1 mRNAs expression. This is the first report on the function of melatonin in osteoclasts and on the suppressive effect of melatonin in osteoblasts among vertebrates.
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PMID:Melatonin suppresses osteoclastic and osteoblastic activities in the scales of goldfish. 1239 May 9

Extreme short stature is a cardinal feature of severe osteogenesis imperfecta (OI), types III and IV. We conducted a treatment trial of growth hormone in children with OI and followed linear growth velocity, bone metabolism markers, histomorphometrics, and vertebral bone density. Twenty-six children with types III and IV OI, ages 4.5-12 years, were treated with recombinant growth hormone (rGH), 0.1-0.2 IU/kg per day for 6 days/week, for at least 1 year. Length, insulin-like growth factor (IGF-I), insulin-like growth factor binding protein (IGFBP-3), bone metabolic markers, and vertebral bone density by DXA were evaluated at 6-month intervals. An iliac crest biopsy was obtained at baseline and 12 months. Approximately one-half of the treated OI children sustained a 50% or more increase in linear growth over their baseline growth rate. Most responders (10 of 14) had moderate type IV OI. All participants had positive IGF-I, IGFBP-3, osteocalcin, and bone-specific alkaline phosphatase responses. Only the linear growth responders had a significant increase in vertebral DXA z-score and a significant decrease in long bone fractures. After 1 year of treatment, responders' iliac crest biopsy showed significant increases in cancellous bone volume, trabecular number, and bone formation rate. Responders were distinguished from nonresponders by higher baseline carboxyterminal propeptide (PICP) values (p < 0.05), suggesting they have an intrinsically higher capacity for collagen production. The results show that growth hormone can cause a sustained increase in the linear growth rate of children with OI, despite the abnormal collagen in their bone matrix. In the first year of treatment, growth responders achieve increased bone formation rate and density, and decreased fracture rates. The baseline plasma concentration of PICP was an excellent predictor of positive response.
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PMID:Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: high predictive value of the carboxyterminal propeptide of type I procollagen. 1256 1

A hormonal servomechanism has been proposed to regulate differentiation and function of the endometrial glandular epithelium (GE) in the ovine uterus during pregnancy. This mechanism involves sequential actions of estrogen, progesterone, ovine interferon tau (IFNtau), placental lactogen (oPL), and placental growth hormone (oGH). The biological actions of oPL in vitro are mediated by homodimerization of the prolactin receptor (oPRLR) and heterodimerization of the oPRLR and oGH receptor. The objectives of the study were to determine the effects of intrauterine oPL, oGH, and their combination on endometrial histoarchitecture and gene expression and to localize and characterize binding sites for oPL in the ovine uterus in vivo using an in situ ligand binding assay. Intrauterine infusion of oPL and/or oGH following IFNtau into ovariectomized ewes treated with progesterone daily differentially affected endometrial gland number and expression of uterine milk proteins and osteopontin. However, neither hormone affected PRLR, insulin-like growth factor (IGF)-I, or IGF-II mRNA levels in the endometrium. A chimeric protein of placental secretory alkaline phosphatase (SEAP) and oPL was used to identify and characterize binding sites for oPL in frozen sections of interplacentomal endometrium from pregnant ewes. Specific binding of SEAP-oPL was detected in the endometrial GE on Days 30, 60, 90, and 120 of pregnancy. In Day 90 endometrium, SEAP-oPL binding to the endometrial GE was displaced completely by oPL and prolactin (oPRL) but only partially by oGH. Binding experiments using the extracellular domain of the oPRLR also showed that iodinated oPL binding sites could be competed for by oPRL and oPL but not by oGH. Collectively, results indicate that oPL binds to receptors in the endometrial glands and that oPRL is more effective than oGH in competing for these binding sites. Thus, effects of oPL on the endometrial glands may be mediated by receptors for oPRL and oGH.
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PMID:Ovine placental lactogen specifically binds to endometrial glands of the ovine uterus. 1260 25

Glucocorticoids (GCs) modulate insulin-like growth factor action in cartilage through mechanisms that are complex and insufficiently defined, especially in the context of cranio-facial growth. Because the family of IGF-binding proteins (IGFBP-1 to -6) is important in the regulation of IGF availability and bioactivity, we examined the effect of GCs on chondrocyte differentiation in correlation with IGFBP production in cultured fetal rat chondrocytes isolated from nasal septum cartilage of fetal rat. Dexamethasone (DEX) effects were tested before and at the onset of extracellular matrix maturation. DEX induced a dose-dependent increase in the size of cartilage nodule formed, (45)Ca incorporation into extracellular matrix, alkaline phosphatase activity, and sulfatation of glycosaminoglycans, maximal effects being obtained with a 10-mM DEX concentration. The IGFBPs produced by cultured chondrocytes were characterized in culture medium which had been conditioned for 24 h under serum-free conditions by these cells. Western ligand blotting with a mixture of [(125)I]IGF-I and -II revealed bands of 20, 24, 29, a 31-32 kDa doublet and a 39-41 kDa triplet which were differently regulated by DEX. Immunoblotting showed that following DEX exposure, IGFBP-3 and -6 were up-regulated whereas IGFBP-2, -5, and the 24 kDa band were down-regulated. The effect of DEX on both differentiation and IGFBP production showed a same dependence, and developed when extracellular matrix maturation had been just induced. The results obtained in this chondrocyte culture system show that production of IGFBPs is modulated by DEX at physiological concentrations thus regulating IGF availability and action, a control which could promote the primordial role of the rat nasal septum in craniofacial growth.
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PMID:Regulation by glucocorticoids of cell differentiation and insulin-like growth factor binding protein production in cultured fetal rat nasal chondrocytes. 1261 30


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