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 have previously demonstrated that RGD peptides prevent tubular obstruction in ischemic acute renal failure (ARF) suggested that exposed unoccupied integrin receptors represent the target for such therapy. The present study investigated the topography of RGD binding sites and integrin receptors in ischemic rat kidneys. Two RGD peptides were synthesized: a cyclic biotinylated (Bt) RGD peptide and a linear RGD peptide (GRGDSP) labeled with rhodamine green (RhoG). Rats were subjected to 45 minutes of renal artery occlusion kidneys were harvested at different times post-ischemia, and stained with RGD peptides and a panel of antibodies to integrins. In control, Bt-RGD staining was undetectable in alkaline phosphatase histochemistry, whereas immunofluorescence detection with Rho-streptavidin conjugate as well as RhoG-GRGDSP staining faintly decorated the basolateral aspect of the proximal tubular cells in a punctate fashion. In contrast, ischemic kidneys showed binding to the basolateral and apical aspects of proximal tubules, peritubular capillaries, and desquamated cells within tubular lumen. The most conspicuous staining of ischemic kidneys was obtained with antibodies to the beta 1 (labeling of the apical aspect of proximal and distal tubules, as well as desquamated cells obstructing tubular lumen) and the alpha V (glomeruli, tubular epithelia, intima of blood vessels stained faintly, while the obstructing cellular conglomerates showed intense staining) subunits. Double staining with Bt-RGD and antibodies against the beta 1 and alpha V beta 3 integrins showed co-localization of staining within the tubules and vasculature, respectively. In vitro attachment of HL-60 leukocytes to the endothelial cells was inhibited by the cyclic RGD peptide. In conclusion, expression of RGD binding sites and beta 1 integrin subunits along the apical aspect of tubular epithelia and on the surface of desquamated cells is in concert with the hypothesis on the pathogenetic role of RGD-recognizing integrins in tubular obstruction. The expression of RGD binding sites along the intimal surface of blood vessels in ischemic kidneys suggests an additional target for RGD peptides in vascular endothelial cells.
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PMID:Two novel probes reveal tubular and vascular Arg-Gly-Asp (RGD) binding sites in the ischemic rat kidney. 921 51

The aim of the study was to determine if pretreatment with misoprostol (a prostaglandin analogue) or nifedipine (a calcium antagonist), know protectants of the whole liver, would ameliorate the ischemia-reperfusion injury (IRI) of resected liver associated with vascular occlusion. Male Wistar rats were allocated to 5 groups (n = 20 each group): sham-operated, liver resection only, liver resection plus pretreatment with 0.1 mg/kg misoprostol, 10 mg/kg, or 2 mg/kg nifedipine during the 3 days before IRI with liver resection. Fifteen percent of the liver was made ischemic by 30-minute continuous vascular occlusion, and the remaining 85% nonischemic liver was resected. The model was designed to have survival of the rats so that liver function could be studied over 3 weeks. Seventeen of 20 control resection rats survived indicating a suitable model for study. The bilirubin level was reduced by 25% on postoperative days 3 through 23 with misoprostol. The serum alanine aminotransferase (ALT) peak was significantly lower on day 1 with misoprostol and high-dose nifedipine (both reduced to half the control resection value). There was a modest but significant reduction of serum alkaline phosphatase (SAP) for low-dose nifedipine on days 1, 2, and 23. Prothrombin had a lower peak and lower values on days 1 through 4 with misoprostol. Liver histological changes were minor, being cytoplasmic vacuolization only, and was slightly more marked in the nifedipine groups. Preoperative misoprostol 0.1 mg/kg and nifedipine 10 mg/kg each ameliorate the IRI associated with liver resection, as measured by liver function tests. Different aspects of liver function were altered by the different agents. These results justify initiating a trial for human liver resections.
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PMID:Hepatic ischemia-reperfusion injury modification during liver surgery in rats: pretreatment with nifedipine or misoprostol. 934 87

The effect of the reversible and relatively irreversible ischemia induced acute renal failure (ARF) in the activities of alkaline phosphatase (AlkPase) and gamma-glutamyltransferase (GGTase) after early (15-30 min) and prolonged (45-60 min) ischemia in the homogenates, and the brush-border membranes (BBM) from rat renal whole, superficial (SC), and juxtamedullary (JMC) cortices were studied. The enzyme activities declined progressively in proportion to the duration of ischemia. Early blood reflow of 15 min to the ischemic rats caused a further decrease in the enzyme activities. However, prolonged reflow (up to 120 min) resulted in partial reversal of the ischemic effect in the early but not in the prolonged ischemic rats. The decrease in the enzyme activities was due to the loss of membrane-bound enzyme components from the damaged BBM into the supernatant fraction as membrane-free enzymes. The activities of AlkPase and GGTase were significantly more decreased by the ischemia in the brush-border membrane vesicles (BBMV)-JMC than in BBMV-SC. The rate of recovery due to reflow for AlkPase was greater in BBMV-SC than apparently for GGTase in BBMV-JMC in early ischemic (15-30 min) rats.
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PMID:Effect of reversible and irreversible ischemia on marker enzymes of BBM from renal cortical PT subpopulations. 943 72

Vascular endothelial growth factor (VEGF) is a major angiogenic growth factor. Angiogenesis stimulated by VEGF occurs in several important clinical contexts, including myocardial ischemia, retinal disease, and tumor growth. The level of VEGF is increased in several skin disorders and is stimulated by ischemia. Tissue expansion has been shown to induce angiogenesis and ischemia on the overlying skin. We therefore investigated the hypothesis that VEGF was expressed in expanded tissue. Three samples of skin were obtained from five patients who sustained reconstruction with tissue expansion. One sample was taken on the implantation site of the expander before implantation. Two samples were taken at the time of removal, respectively, one on the nonexpanded skin adjacent to the expanded area and one on the expanded skin on the site of expansion. On these samples we performed immunolocalization of VEGF. Mouse monoclonal antibody was used, recognized with rabbit anti-mouse immunoglobulin alkaline phosphatase-anti-alkaline phosphatase (APAAP) complex conjugated and revealed with naphthol red. Our results showed clearly an increased number of cells that fixated VEGF antibody on the site of expansion. Cell counts revealed that the numbers of cells expressing VEGF were statistically higher in expanded tissue than in nonexpanded tissue. Before expansion skin specimens did not express VEGF. These findings are the first to show the presence of a growth factor in expanded tissue. They open a new field of research on the biological explanation of tissue-expanded angiogenesis.
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PMID:Vascular endothelial growth factor expression in expanded tissue: a possible mechanism of angiogenesis in tissue expansion. 946 72

Cellular redox status and membrane protein activities were analyzed in kidneys from rats with ischemic acute renal failure (ARF). ARF was induced by clamping the left renal artery for 50 min. A parallel group of control animals was processed. In the ischemic group urea plasma levels were statistically increased as compared with the control group. Studies employing whole kidney homogenates revealed that ischemia produces an increment in lipid peroxidation levels and a reduction in glutathione concentration and in superoxide dismutase and glutathione peroxidase activities. Since lipid peroxidation may alter the function of membrane proteins we determined succinate cytochrome c reductase (SuccR), sodium-potassium ATPase (Na-K-ATPase), glucose-6-phosphatase (G-6-Pase) and alkaline phosphatase (ALP) activities in whole renal homogenates. Only G-6-Pase and ALP activities were modified by ischemia. Since ALP is a brush border membrane (BBM) enzyme and BBM is one of the main target structures in ARF, we assessed some parameters of BBM functionality. ALP, gamma-glutamyl transferase (gamma-GT) and 5'-nucleotidase (5'-NT) showed diminished activities in BBM from ischemic kidneys. Ischemia also modified the Vmax of paraaminohippuric acid (PAH) uptake without altering Km. An increment of lipid peroxidation and membrane fluidity in BBM was observed after the treatment. Total membrane proteins and protein recoveries in BBM were similar in both experimental groups. Sialic acid and sulfhydryl levels were similar in BBM from ischemic kidney and control ones. In summary, ARF induced by renal artery clamping for 50 min takes place with a significant increase in urea plasma levels. A decrease in the antioxidant defense system is detected. This induces lipid peroxidation in whole renal tissue, which may justify the diminished activities of some membrane enzymes such as G-6-Pase and ALP. A specific analysis of BBM function reveals a significant increment of lipid peroxidation which may be the cause of an increased membrane fluidity. This latter parameter might be, at least in part, responsible for the damaged function of apical ALP, 5'-NT, gamma-GT and PAH carrier.
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PMID:Impairment of cellular redox status and membrane protein activities in kidneys from rats with ischemic acute renal failure. 968 97

Mucosal pH abnormalities are associated with anastomotic dehiscence, ischemia, and malignancy. We postulated that intraluminal pH influences intestinal epithelial motility, proliferation, and differentiation and studied extracellular pHo (7.0-8.5) effects on human (Caco-2) intestinal epithelial motility, proliferation, and differentiation. Mucosal healing was modeled by sheet migration and differentiation by alkaline phosphatase and dipeptidyl dipeptidase specific activity. In parallel differentiation and motility studies, we inhibited proliferation with mitomycin to dissociate indirect mitogenic effects. Intracellular pHi was quantitated using BCECF/AM at varying extracellular pHo and in migrating cells. Motility was maximal at pHo 7.6 and proliferation at 7.2. Each decreased with acidity and alkalinity. By contrast, brush border enzyme activity was lowest at pHo 7.0 and highest at pHo 8.5. pHi was highest at pHo 8.5. Migrating cell pHi was higher than static cell pHi. Thus, extracellular pHo deviations perturb Caco-2 pHi homeostasis and motility. Alkalinity promotes differentiation while acidity induces proliferation and limits differentiation.
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PMID:Differential effects of mucosal pH on human (Caco-2) intestinal epithelial cell motility, proliferation, and differentiation. 969 Mar 92

Distal muscle flap ischemia and necrosis is a recognized complication of acute elevation of large skeletal muscle flaps. The aim of this study was to investigate whether the angiogenic properties of platelet derived growth factor (PDGF) could be used to augment skeletal muscle flap survival through the induction of new blood vessel formation before flap elevation. We compared this form of flap augmentation with that achieved by subjecting the muscle to a bipedicled vascular delay procedure. The animal model used was the latissimus dorsi muscle of the male homozygous (hr/hr) hairless mouse. Four groups of animals were investigated in this study (n = 10 per group). Group 1 was the control group in which the entire muscle was elevated as a thoracodorsally based island flap. In group 2, the muscle was subjected to a bipedicled vascular delay procedure. In group 3, the muscle was treated with 500 microg of recombinant human platelet derived growth factor BB. In group 4, the muscle was treated with placebo. Ten days later the entire latissimus dorsi muscle was elevated as a thoracodorsally based island flap in groups 2, 3, and 4. Percentage muscle flap survival was quantitated in all groups 5 days after elevation of the entire muscle. Angiogenesis was then quantitated by analyzing capillary to muscle fiber ratios after alkaline phosphatase staining of representative latissimus dorsi muscle samples from the proximal, middle, and distal flap segments. Percentage muscle flap survival was significantly better in PDGF treated muscles when compared with the vascularly delayed muscles (p < 0.001). Histologic analysis of latissimus dorsi muscle flaps demonstrated a significantly greater number of capillaries in the middle (p < 0.001) and distal (p < 0.001) flap segments of PDGF-treated flaps when compared with the vascularly delayed flaps. Treatment of skeletal muscle with PDGF before flap creation resulted in survival of the entire muscle flap. Our results suggest that this survival may be secondary to PDGF-induced angiogenesis.
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PMID:Augmentation of skeletal muscle flap survival using platelet derived growth factor. 970 77

Capillaries are nonuniform thin tubes: The arteriolar and venular capillary portions express alkaline phosphatase (AP) and dipeptidyl peptidase IV (DPPIV), respectively. Differences in enzyme activities between arteriolar and venular capillary portions could be shown by staining sections of cardiac tissues for AP and DPPIV after coronary infusion of microspheres and by staining cultured endothelial cells that had been collected from coronary microvessels. Through use of a double staining method for AP and DPPIV, adaptive changes in the capillary network were studied in rat hearts exposed to cold, exercise, hypertension, chronic coronary occlusion, and transient coronary occlusion followed by reperfusion. Two patterns could be seen in the adaptations of the ventricular capillary network. The increase in the venular capillary portions is accompanied by remarkable increases in capillary density and capillary-to-myocyte ratio. The increase in the arteriolar capillary portion seemed to be accompanied by a decrease or only a limited increase in capillary density in stressed hearts. The increase in the total capillary density improves the capacity for oxygen transport to tissues with a high tissue perfusion and a short diffusion distance for oxygen. The increase in the arteriolar capillaries may also improve oxygen transport by increasing the arterial blood perfusing the tissue. This seems, however, a compensation for the limited angiogenesis: The alleviation of stresses, such as pharmacological treatment of the hypertrophied heart and reperfusion after transient ischemia, increases venular capillary portions and capillary density. These changes are discussed with immunohistochemical observations of rapid and prolonged expressions of angiogenic growth factors.
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PMID:Adaptive changes in the capillary network in the left ventricle of rat heart. 975 39

The cDNA coding for the transcriptional repressor protein Kid-1 was cloned in a screen for zinc finger proteins, which are regulated during renal development and after renal ischemia. Kid-1 mRNA levels increase in the course of postnatal renal development and decrease after acute renal injury caused by ischemia or administration of folic acid. We have raised a monoclonal anti-Kid-1 antibody and demonstrate that the Kid-1 protein is strongly expressed in the proximal tubule of the adult rat kidney. During nephron development, the Kid-1 protein appears after the S-shaped body stage concomitantly with the brush-border enzyme alkaline phosphatase. In two animal models of polycystic kidney disease, the expression of Kid-1 is downregulated. The loss of expression of Kid-1 in cyst wall cells correlates with the loss of alkaline phosphatase histochemical staining. Kid-1 mRNA levels are also reduced in rodent renal cell carcinomas, another condition characterized by epithelial cell dedifferentiation and increased proliferation. We propose that Kid-1 plays an important role during the differentiation of the proximal tubule.
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PMID:Kid-1 expression is high in differentiated renal proximal tubule cells and suppressed in cyst epithelia. 984 10

The effects of intraportal administration of prostaglandin E1 (PGE1) on portal venous flow, hepatic arterial flow, peripheral tissue blood flow, and systemic arterial flow before and after 60 min total liver ischemia followed by 70% partial hepatectomy in rats were investigated. Total liver ischemia was induced by occluding the hepatoduodenal ligament for 60 min. PGE1 at a dose of 0.5 microg/kg/min was infused intraportally for 15 min before inducing hepatic ischemia (preischemic period) and for 60 min after ischemia (postischemic reperfusion period) in the treatment group. Normal saline was infused in the control group. Seventy percent partial hepatectomy was performed during ischemia. Serum biochemical analysis and liver tissue histology were carried out 1, 3, and 24 h, and 1 and 24 h after reperfusion respectively. One-week survival of the PGE1 group was improved to 70% compared to that of the control group of 30%. Postischemia reperfusion values of portal and peripheral tissue blood flows in the PGE1 group were 6.33 +/- 0.600 ml/min and 27.2 +/- 23.5 (arbitrary), and were significantly different from those of the control group of 4.34 +/- 0.400 ml/min and 23.5 +/- 5.54 (arbitrary), respectively. There was no significant difference in hepatic arterial flow between the two groups. Serum alkaline phosphatase decreased significantly in the prostaglandin group. Histological examination revealed a significant portal venous congestion in the control group 1 and 24 h after reperfusion. The extent of the sinusoidal congestion was also severe in the control group 24 h after reperfusion. It was concluded that PGE1 has a protective effect against liver damage when the liver was injured by warm ischemia and reperfusion followed by partial resection.
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PMID:The effects of intraportal administration of prostaglandin E1 on liver ischemia and hepatectomy in rats. 993 94


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