ABSTRACT
The influence of the cellular cholesterol content on the cytotoxicity of endovanilloids acyldopamines was studied in MDA-MB-231 and MCF 10A cells. The activity of acyldopamines depends on the cellular cholesterol content, and a decrease in cholesterol content increases the cytotoxicity of acyldopamines.
Subject(s)
Atorvastatin/pharmacokinetics , Breast Neoplasms/pathology , Cholesterol/metabolism , Dopamine/analogs & derivatives , Anticholesteremic Agents/pharmacology , Apoptosis , Atorvastatin/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Dopamine/pharmacology , Female , Humans , Receptors, Cannabinoid/metabolism , Tumor Cells, CulturedABSTRACT
Sulfation of N-acyl dopamines has been shown for the first time in cytosolic fractions of rat liver and nervous system. Sulfation of dopamine amides of docosahexaenoic and oleic acids occurred in all tissues studied, N-arachidonoyl dopamine was sulfated in the liver and spinal cord, and N-stearoyl dopamine was sulfated only in the liver. Depending on the substrate and tissue, the sulfation activity varied from 0.5 to 3.5 nmol/min per mg total protein. Kinetic parameters of N-docosahexaenoyl dopamine sulfation in the brain were determined. The findings characterize the sulfation system as the most productive metabolic pathway of N-acyl dopamines, but the role of this system in the body is unclear because of high K(m) value.
Subject(s)
Arylsulfotransferase/metabolism , Brain/metabolism , Dopamine/analogs & derivatives , Dopamine/metabolism , Fatty Acids/metabolism , Liver/metabolism , Spinal Cord/metabolism , Animals , Arachidonic Acids/metabolism , Cytosol/enzymology , Kinetics , Rats , Rats, Wistar , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry , Stearates/metabolism , Substrate SpecificityABSTRACT
A preparation of nanocomplexes containing recombinant proteins (interferons alpha2b and beta1b, insulin, and human granulocyte colony stimulating factor) and natural polysialic acid (PSA) has been described. The incorporation of protein into the complex changes its electrophoretic mobility. Atomic force microscopy reveals the average size of 23-kD insulin complexes with PSA of 10-20 nm and demonstrates that more than 60% of glycopolymer molecules carry a single protein molecule. Experiments with cultured cells show that cytokines bound to polysialic acid retain their ability to regulate cell proliferation. Insulin bound to PSA has a prolonged hypoglycemic effect in vivo.
Subject(s)
Granulocyte Colony-Stimulating Factor/chemistry , Insulin/chemistry , Interferon-alpha/chemistry , Interferon-beta/chemistry , Nanostructures , Sialic Acids/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Electrophoresis, Polyacrylamide Gel , Granulocyte Colony-Stimulating Factor/pharmacology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Interferon alpha-2 , Interferon beta-1b , Interferon-alpha/pharmacology , Interferon-beta/pharmacology , Mice , Microscopy, Atomic Force , Rabbits , Recombinant Proteins/chemistry , Recombinant Proteins/pharmacology , Sialic Acids/pharmacologyABSTRACT
Methods of selective and nonselective covalent immobilization of genetically engineered proteins on molecules of natural polysialic acid are described by the example of human insulin. Such modification increases insulin lifetime in vivo.
Subject(s)
Insulin/chemistry , Sialic Acids/chemistry , Humans , Recombinant Proteins/chemistryABSTRACT
The effects of GABA - docosahexaenoyldopamine (DHED) conjugate on the cerebral haemodynamics and thrombocyte aggregation were evaluated and compared to these of docosahexaenoyldopamine alone. The GABA - DHED conjugate was shown to significantly enhance the cerebral circulation in rats with a model of global transient cerebral ischemia, as compared to the intact animals. Administered alone, DHED increased the blood supply of both intact and ischemic brains to an equal extent. The GABA-DHED conjugate demonstrated the antiaggregative activity, but the effect was less expressed than that of DHED alone.
Subject(s)
Cerebrovascular Circulation/drug effects , Dopamine/analogs & derivatives , Platelet Activating Factor/drug effects , gamma-Aminobutyric Acid/analogs & derivatives , Animals , Dopamine/pharmacology , Humans , Male , Rats , gamma-Aminobutyric Acid/pharmacologyABSTRACT
N-Docosahexaenoyl dopamine exhibited antioxidant activity in the test with a stable oxygen radical galvinoxyl. This compound produced a dose-dependent protective effect on cultured granular cells from rat cerebellum under conditions of oxidative stress. N-Docosahexaenoyl dopamine decelerated the development of symptoms of Parkinson's disease in mice receiving neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Subject(s)
Antioxidants/pharmacology , Cerebellum/physiology , Dopamine/analogs & derivatives , Neuroprotective Agents/pharmacology , Animals , Cells, Cultured , Cerebellum/cytology , Cerebellum/drug effects , Dopamine/pharmacology , Dose-Response Relationship, Drug , Neurons/drug effects , Neurons/physiology , Oxidative Stress/drug effects , Parkinsonian Disorders/physiopathology , RatsABSTRACT
Choline and N,N-dimethylaminoethyl esters of arachidonic and some other fatty acids were synthesized. Experiments on the embryos and larvae of sea urchins, sensitive to cholinergic compounds, showed that arachidonoylcholine exhibited cholinomimetic activity similar to that of nicotine whereas N,N-dimethylaminoethyl arachidonate acted as an acetylcholine antagonist. The corresponding esters of docosahexaenoic acid displayed similar biological properties.
