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)

In order to achieve further information on the in vitro behaviour of osteoblasts derived from osteopenic bone, in the present study comparative measurements of some parameters of cell proliferation, metabolism and differentiation and also of the pericellular partial oxygen pressure (pO2) were performed on normal and osteopenic bone derived osteoblasts from heathy and osteopenic rats. The respiration rate was increased in osteoblasts derived from osteopenic bone as compared to normal cells at 48 hours and 7 days, involving a significant decrease in pericellular pO2 in the culture medium. At 48 hours, in osteopenic bone-derived cells, a significant increase in MTT and a significant decrease of osteocalcin were observed. At 7 days, cell count highlighted a significant slowing down of the proliferation of osteopenic bone-derived osteoblasts. No significant differences were observed for alkaline phosphatase activity, nitric oxide and type I collagen production. The present preliminary results may be taken into consideration also in in vitro comparative biocompatibility or osteointegration studies of biomaterials in normal and osteopenic bone-derived cells because a decrease in pericellular pO2 in these tissue cultures could influence results on material behaviour.
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PMID:Pericellular partial oxygen pressure (pO2) measurement in osteopenic bone-derived osteoblast cultures. 1135 37

When osteoblasts are cultured on surfaces of increasing microroughness, they exhibit decreases in proliferation, increases in differentiation and local factor production, and enhanced response to 1alpha,25(OH)(2)D(3). The cells interact with surfaces through integrins, which signal by the same pathways used by 1alpha,25(OH)(2)D(3), including protein kinase C via phospholipase C and protein kinase A via phospholipase A(2). This provides opportunities for crosstalk that may contribute to the synergistic effects of surface roughness and the vitamin D metabolite. Because these pathways converge at mitogen-activated protein kinase (MAPK), we tested the hypothesis that the extracellular signal-regulated kinase (ERK1/2) subclass of MAPKs mediates the effects of surface roughness and 1alpha,25(OH)(2)D(3). MG63 osteoblast-like osteosarcoma cells were cultured on commercially pure Ti disks with various surface roughnesses: pretreatment (PT; 0.6 microm average roughness [Ra]), coarse grit-blasted and acid-etched (SLA; 4 microm RA), and titanium plasma-sprayed (TPS; 5.2-microm R(a)). At confluence, cells were treated for 24 h with control media or media containing 10(-7) M 1alpha,25(OH)(2)D(3). One-half of the cultures received 1 microm or 10 microm PD98059, a specific inhibitor of the ERK family of MAPKs. PD98059 alone did not affect proliferation, osteocalcin production, or production of transforming growth factor-beta1 or nitric oxide, regardless of the surface roughness. Alkaline phosphatase was reduced by the inhibition of the ERK family kinases on all surfaces to a comparable extent. However, when PD98059 was added to the cultures with 1alpha,25(OH)(2)D(3), the effects of the seco-steroid were blocked, including the synergistic increases seen in MG63 cells cultured on SLA or TPS. These results indicate that ERK1/2 MAPK is required for the maintenance of alkaline phosphatase at control levels and that the effects of 1alpha,25(OH)(2)D(3) are mediated by ERK1/2. However, the effects of surface roughness are not due to the ERK family of MAPKs. This suggests that alternative pathways may be used, including those mediated by other MAPK subclasses.
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PMID:Osteoblast response to titanium surface roughness and 1alpha,25-(OH)(2)D(3) is mediated through the mitogen-activated protein kinase (MAPK) pathway. 1137 60

A therapeutic role of amino acids L-lysine (Lys) and L-arginine (Arg) in osteoporosis and fracture healing was demonstrated previously by in vivo studies. In the present study, primary cultures of osteoblasts were used to investigate the effect of amino acids on gene expression (alkaline phosphatase activity, ALP; osteocalcin, OC; type I collagen), nitric oxide production (NO) and proliferation (MTT) of cells. Cells were isolated from the distal femurs of normal and osteopenic rats. Normal and osteopenic bone-derived cells were divided into four groups: control, Lys (0.587 mg/mL/d), Arg (0.625 mg/mL/d), and Lys + Arg (0.587 + 0.625 mg/mL/d). No evidence of differences between normal and osteopenic bone-derived cultures in basal conditions was observed. A significant (P = 0.002) increase of 10.4% in NO production was observed in normal bone-derived osteoblasts treated with Lys + Arg when compared to the control group at 7 days. At the same time, normal bone-derived osteoblasts treated with Arg and Lys + Arg showed significant increases in type I collagen synthesis of 25.3% and 28.4%, respectively, when compared to the control group. Osteopenic bone-derived osteoblasts showed significant (P = 0.002) increases of 27.6% in MTT and 28.7% in cell count at 48 hours when treated with Lys + Arg in comparison with the control group. At 7 days, NO production and type I collagen synthesis increased significantly (P< 0.005) both in osteopenic bone-derived osteoblasts treated with Arg (NO: 18.5%; type I collagen: 34.4%) and Lys + Arg (NO: 23.7%; type I collagen: 20.9%) compared to the control group. Finally, a significant (P = 0.025) decrease of 5.8% in OC level was observed in osteopenic bone-derived osteoblasts treated with Arg. Results suggest that the potential therapeutic effect of Lys and Arg on bone could be related, at least in part, to an improvement of NO production and type I collagen synthesis by osteoblasts both in normal and in osteopenic bone. In osteopenic bone-derived osteoblasts this synthetic phase is preceded by an initial increase of cell proliferation.
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PMID:Effect of L-lysine and L-arginine on primary osteoblast cultures from normal and osteopenic rats. 1139 8

The development of new therapeutic strategies and innovative biomaterials for the muscoloskeletal system, stresses the need for researchers to have reliable, easy, less time-consuming and ethical experimental models. The aim of the present study was to characterise an in vitro model of cultured rat femora and test the possibility of using this model in dynamic studies on bone healing. 24 femurs were explanted after 12 rats were killed for other experimental protocols. A standard bone defect was created in the distal femoral condyles and femurs were cultured in GBJb medium. Arginine and lysine were administered daily in the Arg-Lys group. The other femurs were left untreated (Control group). At 1, 7, 14 and 21 days, alkaline phosphatase activity, nitric oxide and calcium were measured on the supernatant. At 21 days, femurs were embedded in polymethylmethacrylate for histomorphometry and microhardness evaluation of the newly formed bone. The current results showed that it was possible to study bone healing in vitro by using cultured bones from adult animals. A process for bone healing was observed also in untreated bones. Moreover, the structural analysis of the cultured bone showed that it had characteristics similar to those of the femurs, when they were embedded in resin immediately after animal sacrifice. The effect of Arg and Lys confirmed data of a previous study, where a faster healing of bone defect and fracture was observed in rabbits after Arg and Lys administration.
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PMID:Bone tissue cultures: an in vitro model for the evaluation of bone defect healing after L-arginine and L-lysine administration. 1149 13

Nitric oxide (NO) is a very small lipophilic molecule which rapidly diffuses and reaches the cytoplasmic components, and results in the activation of diverse biological function. It has been already reported that cultured osteoblasts synthesize NO in response to proinflammatory cytokines and lipopolysaccaride. In terms of the action of NO on bone metabolism, cytokine-induced NO by osteoblast inhibits bone resorption through inducing the apoptosis of osteoclast progenitor cells and suppressing the osteoclast activity. Also, NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine is reported to induce a dose-dependent inhibitory effect on the proliferation of osteoblast-like cell lines MG63 and ROS 17/2.8, which indicate that NO may stimulate cell proliferation. On the other hand, cytokine-induced NO is reported to reduce osteoblast activity significantly in high concentration, as was evidenced by inhibition of DNA synthesis, cell proliferation, alkaline phosphatase activity, and osteocalcin production. Thus, the effect of NO on osteoblast activities is still controversial. In the present study, S-nitroso-N-acetyl-dl-penicillamine(SNAP), NO donor enhanced DNA synthesis of MC3T3-E1 in vitro. This activation seems to be mediated by NO directly because specific NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) partially attenuated the osteoblast proliferation induced by SNAP. On the other hand, the guanylate cyclase inhibitor, LY83583, failed to abolish the effect of SNAP on DNA synthesis of osteoblasts and 8-bromo cyclic guanosine 3',5'-monophosphate(cGMP), substituting for the accumulation of intracellular cGMP in osteoblasts, did not enhance the incorporation of 3H-thymidine(3H-TdR). It is, then, suggested that osteoblast proliferation might be enhanced by NO independently apart from the activation of cytoplasmic guanylate cyclase and cGMP-dependent mechanisms.
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PMID:Effect of nitric oxide on mouse clonal osteogenic cell, MC3T3-E1, proliferation in vitro. 1156 90

Cytokines and nitric oxide (NO) have been implicated in bone loss caused by estrogen deficiency. Here we evaluated the effect of nitric oxide synthase (NOS) inhibitors on the bone particle resorbing activity and TNF-alpha release of cultured peripheral blood monocytes (PBM) obtained from 10 premenopausal (PreM) and 10 postmenopausal (PostM) women. Gonadal status (menopause < 3 yr) was assessed by FSH and estradiol. Bone alkaline phosphatase and N-Telopeptide were significantly increased in PostM. Significant differences between PreM and PostM women were observed in bone mineral density of lumbar spine. The bone particle resorbing activity of PBM cultured in the presence of L-arginine-methyl ester (NAME) or aminoguanidine, NOS inhibitors, was determined by (45)Ca release from rat bone labeled particles. TNF-alpha release was assayed in supernatants by ELISA. (45)Ca release was higher in PostM (p < 0.01) and was enhanced by NAME (p < 0.02). Furthermore, TNF-alpha release from PBM was significantly higher in PostM (p < 0.01). Aminoguanidine significantly increased TNF-alpha release in PreM. Based on these findings and on the evidence that estrogen stimulates NOS, we suggest that estrogen withdrawal may reduce the inhibitory effect of NO on TNF-alpha release. Thus, this increased production of TNF-alpha could contribute to the increased postmenopausal bone turnover.
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PMID:Estrogenic status influences nitric oxide-regulated TNF-alpha release from human peripheral blood monocytes. 1157 73

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to prey immobilization by activation of neuronal adenosine A(1) receptors, suppressing acetylcholine release from motor neurons and excitatory neurotransmitters from central sites. It also exacerbates venom-induced hypotension by activating A(2) receptors in the vasculature. Adenosine and inosine both activate mast cell A(3) receptors, liberating vasoactive substances and increasing vascular permeability. Guanosine probably contributes to hypotension, by augmenting vascular endothelial cGMP levels via an unknown mechanism. Novel functions are suggested for toxins that act upon blood coagulation factors, including nitric oxide production, using the prey's carboxypeptidases. Leucine aminopeptidase may link venom hemorrhagic metalloproteases and endogenous chymotrypsin-like proteases with venom L-amino acid oxidase (LAO), accelerating the latter. The primary function of LAO is probably to promote prey hypotension by activating soluble guanylate cyclase in the presence of superoxide dismutase. LAO's apoptotic activity, too slow to be relevant to prey capture, is undoubtedly secondary and probably serves principally a digestive function. It is concluded that the principal function of L-type Ca(2+) channel antagonists and muscarinic toxins, in Dendroaspis venoms, and acetylcholinesterase in other elapid venoms, is to promote hypotension. Venom dipeptidyl peptidase IV-like enzymes probably also contribute to hypotension by destroying vasoconstrictive peptides such as Peptide YY, neuropeptide Y and substance P. Purines apparently bind to other toxins which then serve as molecular chaperones to deposit the bound purines at specific subsets of purine receptors. The assignment of pharmacological activities such as transient neurotransmitter suppression, histamine release and antinociception, to a variety of proteinaceous toxins, is probably erroneous. Such effects are probably due instead to purines bound to these toxins, and/or to free venom purines.
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PMID:Ophidian envenomation strategies and the role of purines. 1173 31

Tuberculosis is the single most serious infectious disease worldwide. The respiratory tract is the primary site of infection by Mycobacterium tuberculosis(MTB). A number of immunogenic components of the cell wall of MTB, if delivered to the lungs as aerosols, can be used to study the local immune response. The site of deposition of these aerosols can be employed to control their residence time in the lungs. Muramyl dipeptide (MDP) aerosols were delivered to alveolar macrophages in the lungs of rodents. Guinea pig macrophages harvested by bronchoalveolar lavage were examined by differential interference contrast microscopy for morphological changes indicative of activation. Bronchoalveolar lavage fluid was analyzed for the presence of alkaline phosphatase, lactate dehydrogenase, N-acetyl-glucosaminidase (NAG), and total protein content. Rat alveolar macrophages were studied for the production of nitric oxide, by induction of nitric oxide synthase. Twenty-four hours following exposure to an aerosol of MDP, alveolar macrophages exhibited morphological characteristics (spreading and pseudopodia), enzyme activity (NAG 50% above control), and production of the reactive intermediate nitric oxide. Rat macrophages subjected to aerosol exposure to MDP when challenged with a second dose of MDP or lipopolysaccharide exhibited a linear dose response as measured by nitric oxide production. These studies indicate that the topical delivery of an MTB bacterial cell wall component, muramyl dipeptide, results in activation of alveolar macrophages. This approach may be useful in elucidating elements of the immune response to MTB.
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PMID:Aerosol delivery of muramyl dipeptide to rodent lungs. 1174 Dec 41

Extracorporeal shock wave (ESW) is an alternative non-invasive method for the promotion of bone growth and tendon repair. In an animal model, we have reported that ESW promoted bone marrow osteoprogenitor growth through transforming growth factor-beta1 induction. We have further explored the mechanism for the ESW promotion of osteogenesis. Results showed that an optimal ESW treatment at 0.16 mJ/mm(2) for 500 impulses rapidly induced a higher O(2)(-) and ONOO(-) production associated with a decrease of nitric oxide level in 1 h, and induced a higher transforming growth factor-beta1 production in 24 h, and a higher colony-forming units-osteoprogenitor formation in 12 days. The colony-forming units-osteoprogenitor colonies revealed positive staining of bone alkaline phosphatase and turned into bone nodules in 21 days. Early scavenging of O(2)(-) but not Ca(2+), H(2)O(2), or prostaglandin E(2) suppressed osteoprogenitor cell growth and maturation. Scavenging of O(2)(-) by superoxide dismutase raised the nitric oxide level back to the basal level and suppressed ESW-promoted osteoprogenitor cell growth, whereas inhibition of ONOO(-) by urate or NO by N-nitro-l-arginine methyl ester did not affect ESW promotion of osteogenesis, indicating that O(2)(-) acted as an early signal for ESW-induced cell growth. Further studies demonstrated that ESW induced ERK activation, and blockage of O(2)(-) production or inhibition of tyrosine kinase, but not protein kinase A and C inhibitors, suppressed ESW-induced ERK activation. In support that O(2)(-) mediated the ESW-induced ERK activation and osteogenic differentiation, we further demonstrated that scavenging of O(2)(-) by superoxide dismutase and inhibition of ERK activation by PD98059 decreased specific osteogenic transcription factor, core binding factor A1 activation, and decreased osteocalcin expression. Taken together, we showed that ESW-induced O(2)(-) production followed by tyrosine kinase-mediated ERK activation and core binding factor A1 activation resulted in osteogenic cell growth and maturation. Thus, an appropriate modulation of redox reaction by ESW may have some positive effect on the bone regeneration.
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PMID:Superoxide mediates shock wave induction of ERK-dependent osteogenic transcription factor (CBFA1) and mesenchymal cell differentiation toward osteoprogenitors. 1178 11

We examined 170 patients with acute viral hepatitis B (AVH-B) and 10 patients with chronic hepatitis B (CH-B) exacerbation. 85% of them were under 40 years old. During the 12-hour night period we measured urine excretion of nitrites (NO2-) and nitrates (NO3-). It was significantly high in AVH-B but in CH-B exacerbation it did not differ from the controls. ACTH and hydrocortisone blood levels were significantly high in AVH-B and in CH-B exacerbation. Though hydrocortisonemia and nitrituria/nitraturia during AVH-B were both high, the correlation between them was negative due to nitric oxide (NO) synthesis suppression by hydrocortisone. A negative correlation between nitrituria/nitraturia and ALAT, ASAT, bilirubin, alkaline phosphatase, gamma-glutamyl-transpeptidase is an indirect evidence for a protective role of NO against viral hepatitis B.
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PMID:[Changes in synthesis of nitric oxide, blood levels of ACTH and cortisol in viral hepatitis B]. 1181 Nov 11


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