Oxidative metabolism of razuprotafib (AKB-9778), a sulfamic acid phosphatase inhibitor, in human microsomes and recombinant human CYP2C8 enzyme

1-Pyrrolidinecarbothioic acid (2-pyridylmethylene) hydrazide chelates Zn2+ but not Mg2+. This compound is about twice as effective as EDTA for inhibiting alkaline phosphatase from calf mucosa, and approx. 1000-fold more effective than EDTA for inhibiting acid phosphatase from wheat germ. The compound did not inhibit pyridoxine kinase activity in human leucocytes at the highest concentration tested (33 micron). Therefore it may be a useful tool for either examining or eliminating the effects of phosphatases in complex enzyme systems.

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A Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages

Scientific Reports ◽

10.1038/s41598-017-12623-w ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 5

Author(s):

Carian E. Boorsma ◽

T. Anienke van der Veen ◽

Kurnia S. S. Putri ◽

Andreia de Almeida ◽

Christina Draijer ◽

...

Keyword(s):

Acid Phosphatase ◽

Alveolar Macrophages ◽

Tartrate Resistant Acid Phosphatase ◽

Phosphatase Inhibitor

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Erythrophagocytosis in the Liver in Hemolytic Anemias

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100664 ◽

1968 ◽

Vol 26 ◽

pp. 184-185

Author(s):

O. T. Minick ◽

E. Orfei ◽

F. Volini ◽

G. Kent

Keyword(s):

Acid Phosphatase ◽

Oxidative Damage ◽

Phosphatase Activity ◽

Kupffer Cells ◽

Acid Phosphatase Activity ◽

Common Type ◽

Red Cell ◽

Cell Fragments ◽

Reticulo Endothelial System ◽

Important Site

Hemolytic anemias were produced in rats by administering phenylhydrazine or anti-erythrocytic (rooster) serum, the latter having agglutinin and hemolysin titers exceeding 1:1000.Following administration of phenylhydrazine, the erythrocytes undergo oxidative damage and are removed from the circulation by the cells of the reticulo-endothelial system, predominantly by the spleen. With increasing dosage or if animals are splenectomized, the Kupffer cells become an important site of sequestration and are greatly hypertrophied. Whole red cells are the most common type engulfed; they are broken down in digestive vacuoles, as shown by the presence of acid phosphatase activity (Fig. 1). Heinz body material and membranes persist longer than native hemoglobin. With larger doses of phenylhydrazine, erythrocytes undergo intravascular fragmentation, and the particles phagocytized are now mainly red cell fragments of varying sizes (Fig. 2).

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The Demonstration of Human Prostatic Acid Phosphatase (Pap) With Phosphorylcholine

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100090427 ◽

1976 ◽

Vol 34 ◽

pp. 88-89

Author(s):

José A. Serrano ◽

Hannah L. Wasserkrug ◽

Anna A. Serrano ◽

Arnold M. Seligman

Keyword(s):

Acid Phosphatase ◽

Prostate Gland ◽

Prostatic Acid Phosphatase ◽

Human Prostate ◽

Rat Tissues ◽

Specific Substrate ◽

Acid Phosphatases ◽

Lysosomal Acid ◽

Cacodylate Buffer

As previously reported (1, 2) phosphorylcholine (PC) is a specific substrate for prostatatic acid phosphatase (PAP) as opposed to other acid phosphatases, e.g., lysosomal acid phosphatase. The specificity of PC for PAP is due to the pentavalent nitrogen in PC, a feature that renders PC resistant to hydrolysis by all other acid phosphatases. Detailed comparative cytochemical results in rat tissues are in press. This report deals with ultracytochemical results applying the method to normal and pathological human prostate gland.Fresh human prostate was obtained from 7 patients having transurethral resections or radical prostatectomies. The tissue was fixed in 3% glutaraldehyde- 0.1 M cacodylate buffer (pH 7.4) for 15 min, sectioned at 50 μm on a Sorvall TC-2 tissue sectioner, refixed for a total of 2 hr, and rinsed overnight in 0.1 M cacodylate buffer (pH 7.4)-7.5% sucrose.

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Prostatic Acid Phosphatase (PAP) Differentiated Ultracytochemically from Lysosomal Acid Phosphate in the Rat with a PAP/Specific Substrate, Phosphorylcholine

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100115870 ◽

1975 ◽

Vol 33 ◽

pp. 450-451

Author(s):

W. Allen Shannon ◽

José A. Serrano ◽

Hannah L. Wasserkrug ◽

Anna A. Serrano ◽

Arnold M. Seligman

Keyword(s):

Acid Phosphatase ◽

Phosphate Buffer ◽

Prostatic Carcinoma ◽

Prostatic Acid Phosphatase ◽

Chemotherapeutic Agents ◽

Specific Substrate ◽

Acid Phosphate ◽

Lysosomal Acid ◽

Design And Synthesis ◽

New Chemotherapeutic Agents

During the design and synthesis of new chemotherapeutic agents for prostatic carcinoma based on phosphorylated agents which might be enzyme-activated to cytotoxicity, phosphorylcholine, [(CH3)3+NCH2CH2OPO3Ca]Cl-, has been indicated to be a very specific substrate for prostatic acid phosphatase (PAP). This phenomenon has led to the development of specific histochemical and ultracytochemical methods for PAP using modifications of the Gomori lead method for acid phosphatase. Comparative histochemical results in prostate and kidney of the rat have been published earlier with phosphorylcholine (PC) and β-glycerophosphate (βGP). We now report the ultracytochemical results.Minced tissues were fixed in 3% glutaraldehyde-0.1 M phosphate buffered (pH 7.4) for 1.5 hr and rinsed overnight in several changes of 0.05 M phosphate buffer (pH 7.0) containing 7.5% sucrose. Tissues were incubated 30 min to 2 hr in Gomori acid phosphatase medium (2) containing 0.1 M substrate, either PC or βGP.

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Tobacco Mosaic Virus-Infected Tissue

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119375 ◽

1985 ◽

Vol 43 ◽

pp. 510-511

Author(s):

Egbert W. Henry

Keyword(s):

Nicotiana Tabacum ◽

Tobacco Mosaic Virus ◽

Chlorogenic Acid ◽

Mosaic Virus ◽

Host Resistance ◽

Oxidative Metabolism ◽

Leaf Tissue ◽

Vein Clearing ◽

Basal Septum ◽

Concentration Levels

Tobacco mosaic virus (TMV) infection has been studied in several investigations of Nicotiana tabacum leaf tissue. Earlier studies have suggested that TMV infection does not have precise infective selectivity vs. specific types of tissues. Also, such tissue conditions as vein banding, vein clearing, liquification and suberization may result from causes other than direct TMV infection. At the present time, it is thought that the plasmodesmata, ectodesmata and perhaps the plasmodesmata of the basal septum may represent the actual or more precise sites of TMV infection.TMV infection has been implicated in elevated levels of oxidative metabolism; also, TMV infection may have a major role in host resistance vs. concentration levels of phenolic-type enzymes. Therefore, enzymes such as polyphenol oxidase, peroxidase and phenylalamine ammonia-lyase may show an increase in activity in response to TMV infection. It has been reported that TMV infection may cause a decrease in o-dihydric phenols (chlorogenic acid) in some tissues.

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Integrated morphometrical and electron energy loss image analysis in cytochemistry

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100153981 ◽

1989 ◽

Vol 47 ◽

pp. 402-403

Author(s):

W.C. de Bruijn ◽

A.A.W. de Jong ◽

C.W.J. Sorber

Keyword(s):

Image Analysis ◽

Acid Phosphatase ◽

Chemical Analysis ◽

Active Form ◽

List Type ◽

Type Number ◽

Enzyme Cytochemistry ◽

Related Data ◽

Endogenous Peroxidase ◽

Electron Energy Loss

One aspect of enzyme cytochemistry is, whether all macrophage lysosomal hydrolytical enzymes are present in an active form, or are activated upon stimulation. Integrated morphometrical and chemical analysis has been chosen as a tool to illucidate that cytochemical problem. Mouse peritoneal resident macrophages have been used as a model for this complicated integration of morphometrical and element-related data. Only aldehyde-fixed cells were treated with three cytochemical reactions to detect different enzyme activities within one cell (for details see [1,2]). The enzyme-related precipitates anticipated to be differentiated, were:(1).lysosomal barium and sulphur from aryl sulphatase activity,(2).lysosomal cerium and phosphate from acid phosphatase activity and(3).platinum/di-amino-benzidine( D A B) complex from endogenous peroxidase activity.

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vitreal cells and specialized phagocytes in the chick embryo retina: A TEM and SEM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159205 ◽

1990 ◽

Vol 48 (3) ◽

pp. 330-331

Author(s):

M.A. Cuadros ◽

M.J. Martinez-Guerrero ◽

A. Rios

Keyword(s):

Cell Death ◽

Plasma Membrane ◽

Acid Phosphatase ◽

Chick Embryo ◽

Basement Membrane ◽

Sem Images ◽

Intimate Contact ◽

Cellular Processes ◽

Sem Study ◽

Free Cells

In the chick embryo retina (days 3-4 of incubation), coinciding with an increase in cell death, specialized phagocytes characterized by intense acid phosphatase activity have been described. In these preparations, all free cells in the vitreal humor (vitreal cells) were strongly labeled. Conventional TEM and SEM techniques were used to characterize them and attempt to determine their relationship with retinal phagocytes.Two types of vitreal cells were distinguished. The first are located at some distance from the basement membrane of the neuroepithelium, and are rounded, with numerous vacuoles and thin cytoplasmic prolongations. Images of exo- and or endocytosis were frequent; the cells showed a well-developed Golgi apparatus (Fig. 1) In SEM images, the cells was covered with short cellular processes (Fig. 3). Cells lying parallel to or alongside the basement membrane are elongated. The plasma membrane is frequently in intimate contact with the basement membrane. These cells have generally a large cytoplasmic expansion (Fig. 5).

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Studies of Vegetative Plant Tissue Compatibility/Incompatibility: The Role of Acid Phosphatase in Lethal Cell Senescence in an Incompatible Heterograft

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002336 ◽

1980 ◽

Vol 38 ◽

pp. 530-531

Author(s):

Randy Moore

Keyword(s):

Acid Phosphatase ◽

Thick Layer ◽

Cell Necrosis ◽

Enzyme Localization ◽

Vegetative Plant ◽

Cell Autolysis ◽

Graft Interface ◽

System 1 ◽

Thin Fibril

Previous work has indicated that the graft incompatihility between Sedrmi telephoides and Solanum pennellil involves cell necrosis that results In a thick layer of collapsed cells at the graft Interface. This necrotic layer insulates the stock from the scion, which results in abscission of the Sedum scion after 4-6 weeks due to desiccation and starvation. Thus, cell autolysis (which is restricted to Sedum) characterizes the Incompatibility response in this system (1). In order to elucidate the events that lead to cell autolysis, and thus better understand the cellular site and mode of action of cellular incompatibility, the appearance and fate of the hydrolytlc enzyme acid phosphatase (AP) was followed in both the compatible Sedum autograft and the incompatible Sedum/Solanum heterograft. Acid phosphatase was localized by a modified Gomori-type reaction; positive (i.e., including NaF inhibitor) and negative (lacking substrate) controls showed no enzymatic precipitate. Following an initial association with the endoplasmic reticulum (ER) and dictyosomes at 6-10 hours after grafting, AP activity in the compatible Sedum autograft is associated primarily with the plasmalemma (Fig. 1). By 18-24 hours after grafting, the AP activity is restricted to the tono-plast and vacuole (Fig. 2). This strict compartmentation and absence of enzyme from the cytosol is maintained throughout the development of the compatible graft. While AP activity in the incompatible Sedum/Solanum heterograft is Initially similar to the compatible Sedum autograft (i.e., initially found on the ER and dictyosomes), there is a marked difference in enzyme localization in the two graft partners as the incompatibility response develops. As in the compatible autograft, Solanum cells at the graft interface show an Increase in AP activity that Is restricted to the vacuole and tonoplast, with little or no enzyme activity in the cytosol (Fig. 3). In comparable Sedum cells, however, there is a dramatic Increase In AP activity in the cytosol (Fig. h); this cytosollc AP activity is associated with thin fibril-like structures (Fig. 5) measuring approximately 60 A in diameter. This high cytoplasmic AP activity In Sedum cells results in cell autolysis, death, and eventual cell collapse to form the characteristic necrotic layer separating the two graft partners.

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