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:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteogenic protein-1 (OP-1) is a member of the bone morphogenetic protein family and has been shown to induce new bone formation in vivo. In the present study, we determined whether the expression of the IGF system, a significant growth factor system in bone, was altered by OP-1 in primary cultures of fetal rat calvarial cells. Levels of messenger RNA (mRNA) encoding insulin-like growth factor I (IGF-I), IGF-II, IGF-I receptor, and IGF-binding proteins (IGFBP-1 to -6) were determined after OP-1 treatment. The level of total IGF-I mRNA was elevated in an OP-1 concentration (0-1000 ng/ml)-dependent manner, with maximal stimulation of IGF-I mRNA of 2- to 3-fold apparent 24 h after treatment. The increase in the IGF-I mRNA level involved a preferential stimulation of transcripts initiated at start site 2 in the exon 1 promoter. The level of IGF-II mRNA also increased by approximately 2-fold in OP-1 treated cells in a concentration-dependent manner. The level of IGF-I receptor mRNA was not altered by treatment. Whereas IGFBP-1 mRNA was not detected in these cells, IGFBP-2 mRNA was expressed, but the expression was not changed after treatment for 48 h in the concentration range (0-1000 ng/ml) tested. The IGFBP-3 mRNA level was increased slightly 48 h after OP-1 treatment in a concentration-dependent manner. The IGFBP-4, -5, and -6 mRNA levels decreased dramatically in an OP-1 concentration-dependent manner. In addition, coincubation of antisense oligonucleotides corresponding to IGF-I or -II mRNA sequence with OP-1 reduced the OP-1 induced elevation in alkaline phosphatase activity. The present results suggest that the differentiation of rat osteoblastic cells in response to OP-1 is mediated in part by increased IGF-I -II gene expression and alterations in the gene expression of different IGFBPs.
...
PMID:Osteogenic protein-1-mediated insulin-like growth factor gene expression in primary cultures of rat osteoblastic cells. 861 32

Local production of insulin-like growth factor (IGF)-binding proteins (IGFBP) determines the availability of the IGF to the cell and thus regulates IGF action. To find out whether specific patterns of IGFBP gene expression and IGFBP secretion were related to cell growth vs. cell differentiation, expression of IGFBP during long-term culture (21 days, n = 5) of the colon carcinoma cell line Caco-2 was investigated at the mRNA and protein levels. Markers of cell proliferation (increase in DNA, RNA, and protein content) and of differentiation [alkaline phosphatase (AP) activity; creatine kinase (CK) activity] were measured in parallel during long-term culture. IGFBP-2 mRNA expression correlated significantly with markers of proliferation (P < 0.05), whereas IGFBP-3 mRNA expression or IGFBP-3 secretion correlated with markers of differentiation (AP: r = 0.83, P < 0.001; CK: r = 0.45, P < 0.01). Similarly, IGFBP-4 mRNA expression correlated significantly with markers of differentiation (AP: r = 0.34, P < 0.05; CK: r = 0.35, P < 0.05). We hypothesize that IGFBP-3 and -4 are related to differentiation of Caco-2 cells, whereas IGFBP-2 is related to proliferation in Caco-2 cells.
...
PMID:Expression of IGFBP-2, -3, and -4 mRNA during differentiation of Caco-2 colon epithelial cells. 894 82

The present study was performed to examine the effect of natural menopause on serum levels of IGF-I, IGF-binding protein (IGFBP)-2 and -3 as well as on bone mass and lipid metabolism in perimenopausal women. One hundred and twenty-one healthy Japanese women, who were 45-55 years old, were studied (71 premenopausal and 50 postmenopausal women 1-9 years after menopause). Bone mineral density (BMD) was measured at the middle third of the radius by using dual energy X-ray absorptiometry. Serum levels of IGF-I, but not those of IGFBP-2 or -3, were significantly reduced in the postmenopausal group compared with the premenopausal group. One year after menopause, serum IGF-I levels were significantly lower, and the biochemical markers of bone turnover, such as serum total alkaline phosphatase level and urinary calcium to creatinine ratio, were significantly higher than the premenopausal levels. Serum levels of IGF-I, but not those of IGFBP-2 or -3, were positively correlated with BMD. Serum levels of IGFBP-2, but not those of IGF-I or IGFBP-3, were negatively correlated with body mass index and body weight. Finally, serum levels of IGFBP-3, but not those of IGF-I, were positively correlated with serum levels of total cholesterol and triglyceride. The present findings suggest that a rapid decrease in serum IGF-I levels after menopause might be partly involved in bone loss following gonadal failure and that IGFBP-2 and -3 might be related to the regulation of body mass and lipid metabolism during perimenopause respectively, although the mechanisms remain unknown.
...
PMID:Effect of natural menopause on serum levels of IGF-I and IGF-binding proteins: relationship with bone mineral density and lipid metabolism in perimenopausal women. 922 24

To investigate the effects of disease and intensive chemotherapy on bone turnover and growth in children with acute lymphoblastic leukemia (ALL), a longitudinal prospective study was carried out in 22 children, aged 1.2-13.5 yr, enrolled in the Medical Research Council-funded randomized trial of childhood ALL treatment in the UK. We measured lower leg length and markers of bone formation [bone alkaline phosphatase (ALP) and procollagen type I C-terminal propeptide (PICP)], bone resorption [pyridinoline, deoxypyridinoline, and carboxyl-terminal telopeptide of type I collagen (ICTP)], soft tissue turnover [procollagen type III N-terminal propeptide (P3NP)], and the GH axis [IGF-I, IGF-binding protein-3 (IGFBP-3), IGFBP-2, and urinary GH] at 1- to 4-week intervals from diagnosis to week 27 of treatment. In addition, GH-binding protein was measured at diagnosis. At diagnosis, mean SD scores were: bone ALP, -1.84; PICP -1.77; pyridinoline, -1.42; deoxypyridinoline, -1.66; ICTP, -0.42; P3NP, +1.45; GH, +24.4; IGF-I, -1.70; IGFBP-3, -0.88; IGFBP-2, +2.42; and GH-binding protein, -0.69. Bone ALP, PICP, and IGFBP-3 were all correlated (P < or = 0.03). During induction and intensification, there was shrinkage of the lower leg, with decreases in PICP, pyridinoline, ICTP, and P3NP (P < 0.05), whereas IGF-I and IGFBP-3 increased (P < 0.05). After prednisolone was discontinued, bone ALP and collagen markers increased markedly (P < 0.01), but there was no significant change in IGF-I and IGFBP-3. In 12 children who received high dose i.v. methotrexate, postglucocorticoid increases in bone ALP and PICP were less, whereas those in ICTP and P3NP were greater, compared to levels in children who did not receive methotrexate (P < 0.05). We conclude that ALL itself caused GH resistance and low bone turnover. During early intensive chemotherapy, further suppression of osteoblast proliferation and osteoclast activity occurred, not mediated through the systemic GH axis, probably by the direct action of prednisolone on bone. The postglucocorticoid increase in bone turnover was also independent of the GH axis and was modulated by high dose i.v. methotrexate, which depressed osteoblast recovery and enhanced osteoclast activity.
...
PMID:Effects of intensive chemotherapy on bone and collagen turnover and the growth hormone axis in children with acute lymphoblastic leukemia. 974 14

The mechanisms which regulate cell turnover in the intestinal epithelium are incompletely understood. The present study was performed to characterize the role of autocrine IGF system components in intestine epithelial cell proliferation and differentiation comparing rapidly growing crypt cells (IEC-6) with differentiating enterocytes (CaCo-2). The autocrine release of IGF-I, IGF-II and IGFBP-1 through -3 was determined by specific RIAs and western ligand blotting. In addition, binding and growth-promoting activity of insulin, IGF-I and IGF-II was investigated. Enterocytic differentiation was assessed by measuring the brush-border enzymes alkaline phosphatase and sucrase. During IEC-6 growth, the autocrine release of IGF-I and -II increased, whereas IGFBP-2 levels decreased. Specific receptors for IGF-I and IGF-II but not insulin could be detected. IGF-I was 100-fold more potent than insulin to stimulate IEC-6 cell proliferation. In contrast, CaCo-2 cells revealed higher binding of insulin than IGF-I/-II and no release of IGF-I. At switch from CaCo-2 cell proliferation to differentiation a marked increase in the secretion of IGF-II (10-fold), IGFBP-1 (2.5-fold), IGFBP-2 (3-fold), and IGFBP-3 (6-fold) was measured. Our data indicate that IGF system components differentially modulate enterocytic cell proliferation and differentiation.
...
PMID:Differential autocrine regulation of intestine epithelial cell proliferation and differentiation by insulin-like growth factor (IGF) system components. 1022 88

Children with acute lymphoblastic leukaemia (ALL) have reduced bone turnover caused by the disease itself and early intensive chemotherapy, but the effects of later chemotherapy using different drug combinations are uncertain. We report here a longitudinal study on 9 children with ALL randomised to receive an additional third intensification block of chemotherapy, compared with 9 children receiving continuing chemotherapy over the same period. During third intensification, bone alkaline phosphatase, procollagen type I C-terminal propeptide, the carboxyterminal propeptide of type I collagen, procollagen type III N-terminal propeptide and lower leg length all decreased in response to dexamethasone, then returned to (but not beyond) baseline levels after dexamethasone was stopped and other drugs started. These changes were unrelated to circulating insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 or IGFBP-2. In all children, bone alkaline phosphatase remained below the population mean throughout. We conclude that dexamethasone decreased bone and soft tissue turnover, probably through direct effects on target tissues. The postdexamethasone phase of third intensification and continuing chemotherapy had no major deleterious effect on collagen turnover, but there was evidence of continuing suboptimal bone mineralisation.
...
PMID:Effects of a third intensification block of chemotherapy on bone and collagen turnover, insulin-like growth factor I, its binding proteins and short-term growth in children with acute lymphoblastic leukaemia. 1053 79

Children treated for acute lymphoblastic leukemia may develop reduced bone mineral density during treatment, but there is little information on the mechanisms involved. In a prospective, longitudinal study on 15 children with ALL, we undertook serial measurements of markers of bone and collagen turnover, insulin-like growth factor (IGF)-I and its binding proteins (IGFBPs)-3 and -2 during the second year of continuing chemotherapy. In eight patients we also measured lower leg length by knemometry. Height SD scores, lower leg length velocity, IGF-I, and markers of bone collagen turnover did not differ significantly from healthy children. However, bone alkaline phosphatase, a marker of the differentiated osteoblast, was lower (mean SD score, -0.64; p < 0.0001), whereas procollagen type III N-terminal propeptide (P3NP, a marker of soft tissue collagen turnover; mean SD score, +0.93, p < 0.05), IGFBP-3 (mean SD score, +0.76; p < 0.01), and IGFBP-2 (mean SD score, +1.24, p = 0.01) were all higher than in healthy children. IGFBP-3 decreased during episodes of afebrile neutropenia (p < 0.05). Within 3 mo after completion of treatment, bone ALP increased in all eight patients, but collagen markers showed little change. IGFBP-2 returned to normal posttreatment, but P3NP and IGFBP-3 remained significantly elevated compared with healthy children (mean SD scores, +1.51 and +1.36, respectively; p < 0.01). We conclude that continuing chemotherapy was associated with normal growth and bone collagen turnover but enhanced soft tissue collagen turnover. Bone bone alkaline phosphatase was low throughout treatment, which suggests impaired osteoblast differentiation resulting from a direct effect of chemotherapy on bone. Although the effect was reversible, the long-term implications for bone health in survivors remain uncertain.
...
PMID:Bone turnover and growth during and after continuing chemotherapy in children with acute lymphoblastic leukemia. 1100 40

BACKGROUND: Insulin-like growth factor (IGF) system components are important regulators of bone formation. Alterations of individual IGF system components have been described in osteoporosis (OP) patients; however, no study has addressed changes in free IGF-I and in all six IGF binding proteins (IGFBPs). METHODS: A cross-sectional study was performed in 45 OP patients and 100 healthy matched controls. Serum levels of free and total insulin-like growth factor I (IGF-I), IGFBP-1 through -6, intact parathyroid hormone (PTH), 25-OH-vitamin D(3) (25OHD(3)), 1,25-(OH)(2)-vitamin D(3) (1,25-(OH)(2)D(3)), osteocalcin (OSC), bone alkaline phosphatase (B-ALP), and carboxyterminal propeptide of type-I procollagen (PICP) were measured with specific assays. Bone mineral density (BMD) of the lumbar spine was determined by dual-energy X-ray absorptiometry (DEXA). RESULTS: Compared with age- and sex-matched control subjects, OP patients showed a 73% decrease in free IGF-I, a 29% decrease in total IGF-I, a 10% decrease in IGFBP-3, and a 52% decrease in IGFBP-5 levels; they had higher levels of IGFBP-1 (4.1-fold), IGFBP-2 (1.8-fold), IGFBP-4 (1.3-fold), and IGFBP-6 (2.1-fold). Alterations in IGF system components were most evident in 13 OP patients with vertebral fractures in the past 4 years compared to patients without fractures. In OP patients with fractures, the ratio between IGFBP-4 and IGFBP-5 was increased whereas levels of OSC were decreased. CONCLUSIONS: Our data provide strong indirect evidence for a functional connection between circulating IGF system components and bone metabolism and the susceptibility to fractures in OP patients.
...
PMID:Serum levels of insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-1 to -6 and their relationship to bone metabolism in osteoporosis patients. 1255 8

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.
...
PMID:Regulation by glucocorticoids of cell differentiation and insulin-like growth factor binding protein production in cultured fetal rat nasal chondrocytes. 1261 30

The insulin-like growth factor (IGF) system plays an important role in the autocrine and paracrine regulation of bone formation and remodeling. The aim of this study was to evaluate the role of the autocrine IGF system during osteogenic differentiation in rat tibial osteoblasts (ROB) in culture. In this in vitro model, the stages of osteogenesis studied were S1, corresponding to the onset of alkaline phosphatase (AP) expression (days 0-3); S2, coincident with the peak of AP expression in differentiation culture conditions (days 4-6), and S3, corresponding to the onset of mineral deposition in the extracellular matrix (days 7-9). The results showed that conditioned medium of ROB contains greater amounts of IGF-II than IGF-I at all differentiation stages. Both peptides showed the highest concentrations on day 3 of differentiation (end of S1). All IGF-binding proteins (IGFBPs), except IGFBP-1 and -6, were detected, and IGFBP-2 was the most abundant IGFBP present in the conditioned media, and its degradation increased from S1 to S3. By semiquantitative RT-PCR, IGF-I and IGF-II were highly expressed on days 3 and 6, whereas IGFBP-2 was constantly expressed. We focused our study on the role of IGF-II and IGFBP-2 on the synthesis of AP, an early marker of osteoblast maturation. The results showed that a significant increase in AP expression was induced by IGF-II added to the differentiating osteoblasts continuously or in S1 but not in S2 or S3. IGFBP-2 was able to potentiate endogenous and exogenous IGF-II-dependent stimulation of AP activity, and its proteolytic degradation in late stages of osteogenesis (S2 and S3) was highly correlated with the increase of active matrix metalloproteinase-2 in the CM and with the decreased efficacy of IGF-II action. These data suggest that IGFBP-2, at nearly equimolar concentration with IGF-II, plays a potentiating role in IGF-II action on ROB differentiation in vitro.
...
PMID:Potentiating role of IGFBP-2 on IGF-II-stimulated alkaline phosphatase activity in differentiating osteoblasts. 1466 41


1 2 Next >>

---