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Biomedical subjects

I L Sun

Publications and source records attributed to I L Sun.

50 records · Page 3Linked to original sources
PubMed1984

Inhibition of plasma membrane NADH dehydrogenase by adriamycin and related anthracycline antibiotics.

Doxorubicin (adriamycin) is cytotoxic to cells, but the biochemical basis for this effect is unknown, although intercalation with DNA has been proposed This study suggests that the cytotoxicity of this drug may be due to inhibition of the plasma membrane redox system, which is involved in the control of cellular growth. Concentrations between 10(-6) - 10(-7) M adriamycin inhibit plasma membrane redox reactions greater than 50%. AD32, a form of adriamycin which does not intercalate with DNA, but is cytotoxic, also inhibits the plasma membrane redox system. Thus, the cytotoxic effects of adriamycin, which limit its use as a drug, may be based on the inhibition of a transplasma membrane dehydrogenase involved in a plasma membrane redox system.

Animals↗
PubMed1984

The antitumor drug, cis diamminedichloro-platinum, inhibits trans plasmalemma electron transport in HeLa cells.

Transplasmalemma electron transport which stimulates the growth of HeLa cells is inhibited by the antitumor drug cis diammine dichloro platinum II at concentrations which correlate with cytotoxic effects. The less cytotoxic trans diammine dichloro platinum II has very little effect on the transmembrane dehydrogenase. This selectivity contrasts with the similarity of these compounds in binding to DNA. We propose that part of the selective antitumor action of the cis compound can be based on its inhibition of the transplasmalemma dehydrogenase which stimulates growth.

Cell Division↗
PubMed1983

Transformed liver cells have modified transplasma membrane redox activity which is sensitive to adriamycin.

Electron transport across the plasma membrane is found in all cells which have been tested. This activity has been implicated in control of cellular growth, transport and hormone response. In virus transformed cells and tumor cells we find the activity is decreased and becomes sensitive to the antitumor drug adriamycin. Inhibition of transmembrane redox by adriamycin parallels cytoxicity to transformed cells.

Animals↗
PubMed1983

Calmodulin-NADH semidehydroascorbate oxidoreductase interactions of clathrin coated vesicles.

NADH semidehydroascorbate oxidoreductase activity is present in clathrin coated vesicles isolated from rat liver. The activity of the enzyme on the coated vesicles and Golgi apparatus but not that of endoplasmic reticulum is stimulated by calmodulin and is inhibited by three different drugs which are known inhibitors of calmodulin function including trifluoperizine, pimozide and R24571. Extraction of clathrin from the vesicles causes a decrease in activity which can be partially restored when the extracted clathrin is added back. Added calmodulin also restores much of the activity which is lost when the clathrin is removed and the specific activity of added pure calmodulin is similar to that of the crude clathrin on a protein basis. There is a decrease in enzyme activity if coated vesicles or Golgi apparatus are treated with a calcium antagonist (8-[N,N-diethylamino]-octyl-3,4,5-trimethoxybenzoate) (TMB-8). However, the enzyme activity can be recovered to that of the untreated control if calcium (6.0 mM) is added. An additive stimulatory effect on enzyme activity is also observed when both calcium (1.0 mM) and calmodulin (40 micrograms/ml) are present in the vesicles simultaneously. The results show that the NADH-semidehydroascorbate oxidoreductase of coated vesicles and Golgi apparatus have regulatory properties different from those of the microsomal electron transport system. Calmodulin-calcium control mediated through the semidehydroascorbate reductase, may be among the components that regulate Golgi apparatus secretion.

Animals↗
PubMed1982

Insulin control of a transplasma membrane NADH dehydrogenase in erythrocyte membranes.

A study of NADH ferricyanide reductase activity in oriented vesicles or open ghosts of human and porcine erythrocytes shows that the dehydrogenase activity can have three types of orientation in the membrane. There is activity which responds only to acceptors and NADH exclusively on the inside face, or exclusively on the outer surface. There is also activity which requires exposure of both sides of the membrane and thus is transmembranous. The transmembrane activity is inhibited by insulin, whereas the internal and external enzymes do not respond to insulin. The transmembrane dehydrogenase can be a basis for proton transport in the plasma membrane.

Animals↗
PubMed1982

Identification of immunologically distinct antigens in pseudorabies virus.

Antigenic proteins of pseudorabies viruses (PrV) are poorly understood. Proteins from purified PrV and membrane proteins from these viral infected cells, therefore, have been studied by antigenic analysis, using virus neutralization and agargel immunoelectrophoresis tests and by polyacrylamide gel electrophoresis, respectively. The study of crossed immunoelectrophoresis against specific antiviral serum antibodies revealed four immunologically distinct antigens involved in PrV. According to their electromobilities, these four immunologically distinct antigens were designated as Ag 1, Ag 2, Ag 3 and Ag 4. The study of dodecyl sulfate-polyacrylamine gel electrophoresis of a membrane-bound but detergent solubilized viral antigenic complex from PrV infected cells also demonstrated the involvement of four glycoprotein antigens. By interpolations of relative mobilities between known protein markers, the molecular weights of these four glycoproteins were estimated to be 61,500, 68,000, 75,000, and 88,000. Results from two dimentional immunoelectrophoresis seemed to be concordant with those obtained by dodecyl sulfate-polyacrylamide gel electrophoresis. This report, therefore presents results, which strongly suggest antigenic similarities in the virion of PrV and cellular membrane glycoproteins of cells infected by this agent. The molecular weight of these four immunologically distinct antigens, Ag 1, Ag 2, Ag 3 and Ag 4, are presumed to have the following molecular weights of 88,000, 75,000, 68,000 and 61,500, respectively.

Antigens, Viral↗
PubMed1978

Comparison of pseudorabies virus inactivated by bromo-ethylene-imine, 60Co irradiation, and acridine dye in immune assay systems.

Pseudorabies virus infections among animals, especially swine, have become prevalent in the United States in the past few years. The disease in swine is now economically important. Test systems and antigens are being developed for use in control and disease suppression efforts. Pseudorabies virus was inactivated by three methods: chemically, with bromo-ethylene-imine; physically, with 60Co irradiation; and chemically and physically, with 3,9-diaminoacridine dye followed by exposure to white visible light. The antigenicities of the preparations were determined in the presence of specific antibody in immunodiffusion tests and through immunoelectrophoresis. The latter technique permitted quantitation of either antigen or antibody. In the electrophoretic patterns, the antigenic mass in bromo-ethylene-imine preparations was estimated to be 42 mg/ml, the same as in the untreated control material. After 60Co irradiation, 22 mg/ml was present, in comparison with 50 mg/ml in the untreated control antigen. In contrast, 67 mg/ml was present in the acridine dye-light-treated preparation, in comparison with 58 mg/ml in the untreated control material. A possible explanation for the acridine dye-light-treated preparation values is that photodynamic inactivation interferes with viral maturation during the replicative cycle within cells, with a resulting production of a greater amount of antigen, at least some of which is in the form of defective particles.

Acridines↗
PubMed1975

Lipophilic chelator inhibition of electron transport in Escherichia coli.

The lipophilic chelator bathophenanthroline inhibits electron transport in membranes from Escherichia coli. The less lipophilic 1,10-phenanthroline, bathophenanthroline sulfonate, and alpha,alpha-dipyridyl have little effect. Reduced nicotinamide adenine dinucleotide oxidase is more sensitive to bathophenanthroline inhibition than lactate oxidase activity. Evidence for two sites of inhibition comes from the fact that both reduced nicotinamide adenine dinucleotide menadione reductase and duroquinol oxidase activities are inhibited. Addition of uncouplers of phosphorylation before bathophenanthroline protects against inhibition.

Alcohol Oxidoreductases↗
PubMed1971

Superinfection in bacteriophage S13 and determination of the number of bacteriophage particles which can function in an infected cell.

Bacteriophage S13 shows exclusion of superinfecting homologous phage, but the exclusion is only partial. The superinfecting phage can form infectious replicative form deoxyribonucleic acid (RF), can direct protein synthesis, and can form progeny particles even at a superinfection time as late as 60 min after the first infection. Exclusion is also only partial for the closely related phage phiX174. Seven min after the first infection, the exclusion mechanism begins to operate, requiring continuous phage-specified protein synthesis. The gene A protein (required for synthesis of progeny RF) appears to be involved in the exclusion mechanism. In superinfection experiments, it was found that at least 40 phage particles per cell can replicate and can carry out protein synthesis, though the number of sites for binding of RF to the membrane is only about 15 per cell. The results suggest that attachment of RF to a binding site is not required for protein synthesis. Evidence is presented that non-attached parental RF can serve as a template for single-stranded deoxyribonucleic acid synthesis.

Binding Sites↗
PubMedDate not supplied

Recent advances in cancer research: drug targeting without the use of monoclonal antibodies.

Cancer research in drug targeting has focused on the use of monoclonal antibody conjugates of drugs. This paper discusses the use of ligand conjugates of drugs to deliver to receptors on cancer cells. We have used transferrin coupled to adriamycin, and report these conjugates specifically bind and kill cancer cells in culture. Our studies of the mechanism show targeted plasma membranes are compromised for NADH ferricyanide reduction, and targeted cells lose diferric transferrin reductase activity. These results indicate that the binding of transferrin-adriamycin conjugates to transferrin receptors on either isolated plasma membranes or viable tumor cells causes an inhibition of redox reactions that are essential for growth. Since transferrin receptors are endocytosable, ligand-drug conjugates also are delivered to the interior of targeted cells where other mechanisms of killing can be employed. This novel method of drug delivery circumvents the need for monoclonal antibodies, and more investigation of the system may allow a controlled clinical study of its effectiveness.

Animals↗