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V Quemener

Publications and source records attributed to V Quemener.

At least 37 records · Page 2Linked to original sources
PubMed1991

On the degradation and elimination of spermine by the vertebrate organism.

1. Treatment of mice and rats with the polyamine oxidase inhibitor N1,N4-bis-(2,3-butadienyl)-1,4-butanediamine (MDL 72527) causes a gradual accumulation of spermine in the circulation and a decrease of spermidine concentration. 2. Spermine is mainly localized in the red blood cells. 3. Co-administration of 2-(difluoromethyl)ornithine and MDL 72527 enhances considerably the rate and extent of spermine accumulation in the circulation. 4. It is assumed that the increased rate of spermine accumulation by the two drugs is due to the enhancement of cell death, i.e. spermine accumulation is the result of its release into the circulation from dying cells, not due to physiological release. 5. After discontinuation of polyamine oxidase inhibition spermine appears to be gradually transformed into spermidine by red blood cell polyamine oxidase, obviously without transformation into N1-acetylspermine.

Animals↗
PubMed1991

The growth of MAT-LyLu rat prostatic adenocarcinoma can be prevented in vivo by polyamine deprivation.

The combination of inhibitors of ornithine decarboxylase and polyamine oxidase, and of antibiotics suitable for the (partial) decontamination of the gastrointestinal tract, with a polyamine deficient diet, is responsible for the almost complete inhibition of the growth of MAT-LyLu prostatic adenocarcinoma. In the tumor-bearing animals, erythrocyte spermidine levels were reduced, but spermine concentrations were increased. As has been previously observed, the increase in erythrocyte spermine level was associated with an enhancement of malignant cell death. Adriamycin administration did neither diminish tumor growth, nor potentiate the antitumor effect of polyamine deprivation treatment. Interruption of the polyamine deprivation treatment was accompanied by a significant enhancement of tumor growth. Since polyamine deprivation causes only reversible growth inhibition, it seems not appropriate as a monotherapy.

Adenocarcinoma↗
PubMed1991

Biological significance of circulating polyamines in oncology.

Malignant cell proliferation is associated with an increase intracellular polyamine metabolism which itself appears to be in equilibrium with the extracellular circulating polyamine compartments. Erythrocyte polyamine contents may be used clinically as an index of cell proliferation, but the exact biological roles of circulating polyamines, considered as physio(patho)logical parameters involved in the homeostatic(dys)regulation of cell proliferation, remain obscure. It is known that circulating polyamines help promote malignant cell proliferation and metastatic dissemination, but their ultimate targets are not yet completely understood. Either produced by actively proliferating normal or cancer cells, or absorbed from the gastro-intestinal tract (food and colonic microfloral population), circulating polyamines could favour in vivo malignant cell proliferation. 1) Since these organic polycations are more rapidly internalized by cancer cells than by normal ones, do they join and facilitate the malignant intracellular polyamine metabolism? 2) Does binding of polyamines to specific acceptor sites at the surface of cancer cells, thereby modulating endocytosis of biological factors present in the extracellular spaces, modify the homeostatic control of cell proliferation and differentiation? 3) Do modifications of blood polyamine compartmentalization, observed in cancerous organisms, responsible for new enzyme and/or immune capacities, contribute to tumor progression? Answering the above-mentioned questions would lead to new therapeutic approaches in human oncology.

Cell Division↗
PubMed1990

Aldehyde dehydrogenase activity in xenografted human brain tumor in nude mice. Preliminary results in human glioma biopsies.

ALDH activity measured fluorimetrically using a high concentration of aliphatic aldehyde as substrate was studied in human glioblastomas grafted in nude mice. Compared with normal brain, ALDH activity is significantly increased in malignant glioma tissue, especially in the cytosolic subcellular fraction. Correlatively, in comparison with normal brain tissue, MDA levels were significantly reduced in whole homogenates and in cytosolic fractions of xenografted glioblastoma tissue. Preliminary results concerning human malignant glioma biopsies are in good agreement with our experimental data. In view of previous works, these results suggest a relationship between alterations in ALDH iso-enzymes activities and cytosolic aldehyde concentrations with respect to normal or tumoral cell growth.

Aldehyde Dehydrogenase↗
PubMed1990

Inhibition of adenylate cyclase activity by polyamines in human erythrocyte plasma membranes.

Polyamines (spermidine, spermine and putrescine) inhibited the adenylate cyclase activity in a concentration dependent manner in human erythrocyte plasma membranes. Spermidine (Spd) exhibited more inhibitory effect than spermine (Spm) and putrescine (Put). On the contrary, the addition of amino acids (arginine, glutamine and lysine) did not influence the basal enzyme activity. Other cations (polylysine, polyarginine and polyglutamine) also did not affect the enzyme activity. Addition of all the three polyamines (Spd, Spm and Put) in the reaction mixture exhibited moderate inhibitory effect on the adenylate cyclase activity whether it was basal or activated with sodium fluoride or with forskolin. Since the three polyamines exhibited maximum inhibitory effect at 10 microM concentration which is within physiological limit for mammalian tissues, we suggest that there may be a regulatory function of these molecules on adenylate cyclase activity in human erythrocytes.

Adenylyl Cyclase Inhibitors↗
PubMed1990

Red blood cell polyamine level changes following heart transplantation in man.

Follow-up of orthotopic heart transplanted patients has revealed the existence of abnormally high red blood cell (RBC) spermidine (Spd) levels during the first two months after surgical procedure (A-period). From the third month after heart transplantation (B-period), RBC Spd concentrations went back to normal values in early cardiac rejection (ECR) patients. During A- and B-periods, significantly higher Spd levels and Spd/Spm ratios were observed in late cardiac rejecting (LCR) patients than in ECR ones. The lack of a direct relationship between the histological grade of rejection and RBC Spd levels leads us to consider these polyamine blood levels as a new biological instrument in the diagnosis of heart rejection.

Chromatography, High Pressure Liquid↗
PubMed1990

Effects of a series of homologous alpha,omega-dimethylaminoalkanes on cell proliferation: binding and uptake of putrescine by a human glioblastoma cell line (U251) in culture.

The first step of polyamine uptake is the binding of polyamines to the cell membrane. In order to characterize the specificity of the putrescine binding sites at the surface of the glioblastoma cells (U251), we have carried out competition experiments between putrescine bound to latex microspheres and vizualized by scanning electron microscopy and a series of N,N'-tetramethyl-alpha,omega-diaminoalkanes. N,N'-tetramethyl-1,4-butanediamine (N,N'-tetramethylputrescine) and higher homologs inhibit the latex putrescine binding to the cell surface and concomitantly cell proliferation. [14C] putrescine uptake was mainly inhibited by the lower homologs, which were devoid of antiproliferative effects. Our results suggest that putrescine uptake by the human glioblastoma cell line U251, and putrescine binding to the surface of these cells are independent processes. The potential relationship between antitumor effect of N,N'-tetramethyl-alpha,omega-diaminoalkanes and its binding to a specific putrescine acceptor site is discussed.

Binding Sites↗
PubMed1990

Erythrocyte polyamine levels in human prostatic carcinoma.

Abnormally high red blood cell polyamine levels were found in benign prostatic hyperplasia and in prostatic adenocarcinoma patients. In prostatic adenocarcinoma patients a relationship was noted between the importance of red blood cell spermidine and spermine concentrations, and the clinical stage of the disease (Whitmore classification). Considering prostatic adenocarcinoma patient populations, patients with metastases (groups 3 and 4) statistically differed from those without metastases (group 2). Furthermore, red blood cell polyamine level determination discriminated patients in the hormonal escape group (group 4) from those usually considered as hormone responsive (groups 2 and 3). No statistically significant correlation was observed between red blood cell polyamine levels and usual tumor markers (prostatic acid phosphatase and prostate specific antigen). These results confirmed that red blood cell polyamine levels must be considered as a circulating index of cell proliferation that might be of clinical importance during the long-term followup and treatment of prostatic adenocarcinoma patients.

Adenocarcinoma↗
PubMed1990

Mechanism of spermidine uptake in cultured mammalian cells and its inhibition by some polyamine analogues.

Transport pathways for spermidine (Spd) were characterized in mammalian cells in culture of different origin, i.e. L 1210, P 388, C 6, U 251, Balb/c 3T3 normal and transformed by virus SV40 (SV40/3T3). The kinetic constants (Km and Vmax) for 14C-Spd uptake were found to be different in these cells. Spd uptake was inhibited by spermine and putrescine in all cells. Preloading of these cells with system A and other amino acids, including ornithine, usually did not affect Spd uptake, except in L 1210 and C 6 cells, where Spd uptake was accelerated by 2-aminoisobutyric acid, demonstrating that in these two cell lines the polyamines share the system A pathway. Iso-osmotic replacement of Na+ by choline chloride in the assay medium resulted in a decrease in Spd uptake which suggests that Spd uptake is Na+ activated. In all cells, Spd uptake was inhibited by gramicidin and the Ca2+ ionophore A 23187. The degree of inhibition varied among the cells. Valinomycin (K+ ionophore) inhibited Spd uptake by C 6, P 388, Balb/c 3T3 and SV40/3T3 but not by L 1210 and U 251 cells. Treatment with N-ethylmaleimide or p-L 1210, C 6, Balb/c 3T3 and SV40/3T3 cells did not affect appreciably the uptake process. Some newly synthesized polyamine analogues inhibited the Spd uptake of all cells.

Amino Acids↗
PubMed1990

Polyamines and polyamino acids regulation of cytosolic tyrosine protein (Tyr-P) kinase from human erythrocytes.

In vitro regulation of cytosolic tyrosine protein (Tyr-P) kinase from human erythrocytes by polyamines, polyamino acids, negative charged compounds or by insulin using angiotensin II or poly (Glu-Tyr)4:1 as substrates was studied. All the three polyamines, putrescine (Put), spermidine (Spd) and spermine (Spm) stimulated the Tyr-P kinase activity in a dose dependent manner. Spm stimulated Tyr-P kinase activity higher than Put and Spd whether the substrate was angiotension II or poly (Glu-Tyr)4:1. Polyamino acids (polyornithine, polyarginine, polyglutamic acid and polyaspartic acid) did not affect significantly the Tyr-P kinase phosphorylation except polylysine which significantly stimulated the Tyr-P kinase activity. Negative charged compounds (chondroitin sulfate A, B and C) and heparin inhibited the Tyr-P kinase phosphorylation while insulin did not influence the enzyme activity in the presence of either substrates.

Angiotensin II↗
PubMed1990

Coupling of Na+ with the spermidine transporter protein in NIH BALB/c 3T3 cells.

This study demonstrates that polyamine spermidine (Spd) transporter protein is directly coupled with the Na+ in a ternary complex form, Na(+)-Spd-carrier. The Spd is transported with Na+ in a 1:1 stoichiometry relationship. Interestingly, addition of 2-deoxyglucose in the assay medium did not influence significantly the Spd uptake demonstrating the ATP independency of Spd transport.

Adenosine Triphosphate↗
PubMed1990

Mechanism of polyamine spermidine uptake by Xenopus laevis oocytes.

In this study, the mechanisms of polyamine spermidine (Spd) uptake were investigated in Xenopus laevis oocytes. Spd uptake followed a sigmoidal kinetics with [S]90/[S]10 = 3 microM and Hill interaction coefficient (n) = 2. The order of magnitude of uptake and efflux was similar (t1/2 = 45 min). The equilibrium potential for Spd, calculated by Nenrst equation, was 90.78 mV. Free energy change for the uptake (delta G) was found to be 2.31 Kcal/mole of Spd. During efflux, Spd was not converted into putrescine or spermine. It seems that there are two types of Spd uptake pathways: Na(+)-dependent and Na(+)-independent since replacement of Na+ from incubation medium did not completely abolish the Spd uptake. The Na(+)-dependent component of Spd uptake was shared neither by system A nor by system ASC amino acids.

Amino Acids↗
PubMed1989

Role of protein kinase C activators and inhibitors, calmodulin antagonists and membrane sialic acids in polyamine transport in murine leukemia cells.

The effects of activators and inhibitors of protein kinase C (phorbol esters and H-7) and antagonist to calmodulin (TFP) on polyamine transport in murine leukemia (L1210) cells are investigated. Phorbol esters and H-7 are found to enhance and curtail the uptake of 14C-Spermidine (Spd) respectively in L1210 cells. TFP also inhibits the uptake process. After desialation of cells with neuraminidase, phorbol esters are found to further increase the uptake of 14C-Spd by 35% compared to untreated cells. The sialic acid contents of the cells are regenerated by incubation with 14C-glucosamine for 18 hours. The regenerated cells mimic like untreated cells for the uptake of 14C-Spd i.e. after regeneration of sialic acids, the Spd uptake is curtailed significantly in comparison with desialated cells. Phorbol esters are found to enhance the activity of transglutaminase present in L1210 cells while H-7 and TFP exhibit reverse effects. The possible role of phorbol esters, H-7 and TFP and their effects on transglutaminase activity in relation with Spd transport process are discussed.

Animals↗
PubMed1987

Evolution of red blood cell polyamine levels in partially hepatectomized rat.

Erythrocyte levels of polyamines, especially of spermidine are greatly elevated during the course of liver regeneration. In contrast to putrescine and spermine levels, from the tenth hour to the fourth week after partial hepatectomy, correlation has been observed between the elevation of liver and erythrocyte spermidine concentrations. Substituting drinking water with 2% alpha difluoromethylornithine (alpha-DFMO) commencing 48 hr prior to partial hepatectomy and continuing until death, though ineffective in inhibition of liver [3H]-thymidine incorporation, prevented the rise in hepatic putrescine concentrations (without modifying those of spermidine and spermine) and correlatively decreased red blood cell (RBC) spermidine levels. Thus, an excess of liver spermidine produced from an excess of newly synthetized putrescine could be released in blood and taken up by erythrocytes, especially as affinity of RBC for spermidine is at least 30 fold higher than that for putrescine. In vivo the spermidine half-life in RBC was estimated to be 2.5-3.0 hr, which could explain the elevation of erythrocyte and liver spermidine levels. The elevation of erythrocyte spermidine concentration is not correlated to that of the regenerating liver weight but dependent on the extent of partial hepatectomy. The elevation of erythrocyte spermidine concentrations, which appeared to be linked to the cellular proliferating activity, could contribute to determine intratumoral proliferation in cancerous patients.

Animals↗