scholarly journals Inhibition of lipid-linked oligosaccharide synthesis by aryl phosphates

1981 ◽  
Vol 196 (1) ◽  
pp. 71-79 ◽  
Author(s):  
S Kato ◽  
M Tsuji ◽  
Y Nakanishi ◽  
S Suzuki
Keyword(s):  
Direct Effect ◽  
Rat Liver ◽  
Inhibitory Effect ◽  
Oligosaccharide Synthesis ◽  
Phenyl Phosphate ◽  
Dolichyl Phosphate ◽  
Exogenous Substrate ◽  
Nitrophenyl Phosphate ◽  
The Individual ◽  
Related Compounds

Our previous work has shown that phenyl phosphate acts as an exogenous substrate for GDP-mannose:dolichyl phosphate mannosyltransferase in rat liver microsomal fractions to give rise to phenyl phosphate beta-D-mannose, a compound which, unlike Dol-P-Man (dolichyl phosphate beta-D-mannose), cannot act as mannose donor for further mannose-adding reactions in microsomal fractions. The study has now been extended to the action of various aryl phosphates and structurally related compounds on several other glycosyltransferase systems in the microsomal fractions. (1) Examination of the ability of these compounds to accept sugars from various sugar nucleotides indicated that the individual compounds have specificity as sugar acceptors. Thus phenyl phosphate acted as an effective acceptor for both mannose and glucose, whereas benzenephosphonic acid was active only in accepting mannose. p-Nitrophenyl phosphate was a more effective glucose acceptor than phenyl phosphate, but had only 8% of the mannose-accepting activity of phenyl phosphate. (2) Phenyl phosphate had an inhibitory effect on the transfer of mannose form GDP-mannose to lipid-linked oligosaccharides and to glycoproteins in rat liver microsomal fractions. The inhibition depended on the concentration of phenyl phosphate and on the extent of inhibition of Dol-P-Man synthesis. It is proposed that phenyl phosphate has a direct effect on the synthesis of Dol-P-Man and that its inhibition of synthesis of lipid-linked oligosaccharides and glycoproteins could be a consequence of this effect.

scholarly journals Retinyl phosphate mannose synthesis in rat liver membranes. Phospholipase sensitivity and phospholipid requirement

1983 ◽  
Vol 216 (3) ◽  
pp. 727-735
Author(s):  
Y Shidoji ◽  
C S Silverman-Jones ◽  
L M De Luca
Keyword(s):  
Endoplasmic Reticulum ◽  
Enzyme Activity ◽  
Phospholipase C ◽  
Rat Liver ◽  
Membrane Fraction ◽  
Inhibitory Effect ◽  
Synthetic Activity ◽  
Dolichyl Phosphate ◽  
Liver Membranes ◽  
Endogenous Lipids

A remarkable and immediate decrease in GDP-mannose:retinyl phosphate mannosyltransferase activity was found on pre-incubation of rat liver postnuclear membranes with phospholipase A2 or phospholipase C. Under the same conditions of pre-incubation (1 min at 37 degrees C) trypsin did not affect the enzyme activity, whereas pre-incubation for 30 min with trypsin and Pronase abolished enzyme activity. The lipid extract of untreated rat liver membranes partially restored enzyme activity after phospholipase treatment. Sphingomyelin was as active as the endogenous lipids. Other phospholipids were less active in the following order: phosphatidylcholine greater than phosphatidylethanolamine greater than phosphatidylinositol = phosphatidylserine. Dolichyl phosphate mannose synthesis was inhibited less (33%) by phospholipase C than was Ret-P-Man synthesis (98.5%) under identical conditions of incubation, which included 0.025% Triton. However, retinyl phosphate mannose synthesis by purified endoplasmic reticulum was found to be resistant to phospholipase C. Mixing experiments failed to demonstrate an inhibitory effect of the phospholipase-treated postnuclear membrane fraction on the synthetic activity of the endoplasmic reticulum, thus excluding the release of an inhibitory factor from the postnuclear membranes.

Purification and Characterization of Lupus Anticoagulant Like Protein from Agkistrodon Halys Brevicaudus Venom

1996 ◽  
Vol 76 (06) ◽  
pp. 0993-0997
Author(s):  
Zhao-Yan Li ◽  
Xiao-Wei Wu ◽  
Tie-Fu Yu ◽  
Eric C-Y Lian
Keyword(s):  
Amino Acid ◽  
Lupus Anticoagulant ◽  
Inhibitory Effect ◽  
Clotting Factor ◽  
Acid Oxidase ◽  
Crude Venom ◽  
Amino Acid Oxidase ◽  
Sds Page ◽  
The Individual ◽  
Reducing Condition

SummaryBy means of CM-Sephadex C-25, DEAE-Sephadex A-50, Sephadex G-200, and Sephadex G-75 chromatographies, a lupus anticoagulant like protein (LALP) from Agkistrodon halys brevicaudus was purified. On SDS-PAGE, the purified LALP had a molecular weight of 25,500 daltons under non-reducing condition and 15,000 daltons under reducing condition. The isoelectric point was pH 5.6. Its N terminal amino acid sequencing revealed a mixture of 2 sequences: DCP(P/S)(D/G)WSSYEGH(C/R)Q(Q/K). It was devoid of phospho-lipaseA, fibrino(geno)lytic, 5′-nucleotidase, L-amino acid oxidase, phosphomonoesterase, phosphodiesterase and thrombin-like activities, which were found in crude venom. In the presence of LALP, PT, aPTT, and dRVVT of human plasma were markedly prolonged and its effects were concentration-dependent but time-independent. The inhibitory effect of LALP on the plasma clotting time was enhanced by decreasing phospholipid concentration in TTI test. The individual clotting factor activity was not affected by LALP when higher dilutions of LALP-plasma mixture were used for assay. Russell’s viper venom time was shortened when high phospholipid confirmatory reagent was used. Therefore, the protein has lupus anticoagulant property.

scholarly journals Combined Luteolin and Indole-3-Carbinol Synergistically Constrains ERα-Positive Breast Cancer by Dual Inhibiting Estrogen Receptor Alpha and Cyclin-Dependent Kinase 4/6 Pathway in Cultured Cells and Xenograft Mice

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2116
Author(s):  
Xiaoyong Wang ◽  
Lijuan Zhang ◽  
Qi Dai ◽  
Hongzong Si ◽  
Longyun Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cultured Cells ◽  
Inhibitory Effect ◽  
Cyclin Dependent Kinase ◽  
Xenograft Mice ◽  
The Individual

The high concentrations of individual phytochemicals in vitro studies cannot be physiologically achieved in humans. Our solution for this concentration gap between in vitro and human studies is to combine two or more phytochemicals. We screened 12 phytochemicals by pairwise combining two compounds at a low level to select combinations exerting the synergistic inhibitory effect of breast cancer cell proliferation. A novel combination of luteolin at 30 μM (LUT30) and indole-3-carbinol 40 μM (I3C40) identified that this combination (L30I40) synergistically constrains ERα+ breast cancer cell (MCF7 and T47D) proliferation only, but not triple-negative breast cancer cells. At the same time, the individual LUT30 and I3C40 do not have this anti-proliferative effect in ERα+ breast cancer cells. Moreover, this combination L30I40 does not have toxicity on endothelial cells compared to the current commercial drugs. Similarly, the combination of LUT and I3C (LUT10 mg + I3C10 mg/kg/day) (IP injection) synergistically suppresses tumor growth in MCF7 cells-derived xenograft mice, but the individual LUT (10 mg/kg/day) and I3C (20 mg/kg/day) do not show an inhibitory effect. This combination synergistically downregulates two major therapeutic targets ERα and cyclin dependent kinase (CDK) 4/6/retinoblastoma (Rb) pathway, both in cultured cells and xenograft tumors. These results provide a solid foundation that a combination of LUT and I3C may be a practical approach to treat ERα+ breast cancer cells after clinical trials.

scholarly journals Characterization of cathepsins in cartilage

1967 ◽  
Vol 105 (2) ◽  
pp. 549-557 ◽  
Author(s):  
S. Y. Ali ◽  
L. Evans ◽  
E. Stainthorpe ◽  
C. H. Lack
Keyword(s):  
Cathepsin B ◽  
Cartilage Matrix ◽  
Heat Inactivation ◽  
Ph Values ◽  
Fixed Weight ◽  
Exogenous Substrate ◽  
Nitrophenyl Phosphate ◽  
Rabbit Ear ◽  
Ear Cartilage

The presence of a cathepsin B-like enzyme in rabbit ear cartilage was established by the use of the synthetic substrates benzoyl-l-arginine amide and benzoyl-dl-arginine 2-naphthylamide. This was facilitated by using a technique that permits the incubation of a fixed weight of thin (18μ) cartilage sections with an appropriate exogenous substrate. The enzymic properties of cathepsin B in cartilage have been compared with an endogenous enzyme that liberates chondromucopeptide by degrading the cartilage matrix autocatalytically at pH5. Besides being maximally active at pH4·7, these cartilage enzymes are enhanced in activity by cysteine and inhibited by arginine analogues, iodoacetamide, chloroquine and mercuric chloride. They are not inhibited by EDTA, di-isopropyl phosphorofluoridate and diethyl p-nitrophenyl phosphate. When inhibiting the release of chondromucopeptide from cartilage at pH5, the arginine-containing synthetic substrates are hydrolysed simultaneously. These enzymes also share the same heat-inactivation characteristics at various pH values, being stable at acid pH and unstable at neutral and alkaline pH. The experimental evidence indicates that a cathepsin B-like enzyme may be partly responsible for the autolytic degradation of cartilage matrix at pH5.

Time course of dolichol and dolichyl phosphate in regenerating rat liver

Lipids ◽  
1988 ◽  
Vol 23 (1) ◽  
pp. 28-31 ◽  
Author(s):  
Kouji Yamada ◽  
Manabu Murakami ◽  
Kouichi Katayama ◽  
Tadashi Sato
Keyword(s):  
Rat Liver ◽  
Time Course ◽  
Dolichyl Phosphate ◽  
Regenerating Rat Liver

Autoregulation of 3, 3′,5′-triiodothyronine production by rat liver microsomes

1981 ◽  
Vol 98 (2) ◽  
pp. 240-245 ◽  
Author(s):  
T. Kaminski ◽  
J. Köhrle ◽  
R. Ködding ◽  
R.-D. Hesch
Keyword(s):  
Rat Liver ◽  
Incubation Medium ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Incubation Mixture ◽  
Rat Liver Microsomes ◽  
Experimental Conditions ◽  
Physiological Concentration ◽  
Enzyme Binding ◽  
Ph Dependent

Abstract. Conversion of thyroxine (T4) to 3,3′,5′-triiodothyronine (rT3) was studied in rat liver microsomes. Addition of rT3 at a physiological concentration to the incubation medium inhibited the deiodination of thyroxine to rT3. With a concentration of rT3 greater than 37.6 nM no net rT3 production at pH 8.0 was observed. Further increases in rT3 concentration resulted only in degradation of added rT3 and no net synthesis of rT3 from T4 could be detected. The inhibitory effect of rT3 upon its own production from T4 was pH dependent, 5 fold lower amounts of hormone being required to inhibit completely rT3 production at pH 7.4 than at pH 8.0. With the same experimental conditions no significant effect of rT3 on the conversion of T4 to 3,5,3′-triiodothyronine (T3) could be observed at pH 8.0 with all concentrations of added iodothyronine. A linear production of 3,3′-T2 from added rT3 was determined over the whole range of rT3 concentration, suggesting a lack of saturation of deiodinating enzyme. Binding of rT3 by anti-rT3 antibody added to the incubation mixture enhanced rT3 production from T4 by protecting rT3 from being degraded and/or diminishing the inhibitory effect of this iodothyronine on its own production. It was concluded that rT3 influenced its own production and that this effect may represent an important autoregulatory process in the iodothyronine metabolism.

BIOCHEMICAL STUDIES ON TOFRANIL

1961 ◽  
Vol 39 (3) ◽  
pp. 551-558 ◽  
Author(s):  
P. N. Abadom ◽  
K. Ahmed ◽  
P. G. Scholefield
Keyword(s):  
Rat Brain ◽  
Rat Liver ◽  
Brain Cortex ◽  
Respiratory Activity ◽  
Liver Mitochondria ◽  
Brain Mitochondria ◽  
Inhibitory Effect ◽  
Rat Liver Mitochondria ◽  
Brain Cortex Slices ◽  
Cortex Slices

Tofranil inhibits the respiratory activity of rat brain cortex slices incubated in a glucose-containing medium. It also inhibits the uptake and incorporation of glycine-1-C14at concentrations which have only a slight inhibitory effect on the respiration of slices. Tofranil also inhibits oxidative phosphorylation in both rat liver and rat brain mitochondria but at higher concentrations respiration is greatly affected. Tofranil differs quantitatively from chlorpromazine in its greater inhibitory effect on the ATP–Pi32exchange reaction and its lesser effect on the cytochrome c oxidase activity of rat liver mitochondria.

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