acth-(4-7)--pro-gly-pro- and prolyl-glycyl-proline

Topics: Adrenocorticotropic Hormone; Animals; Cell Differentiation; Cell Line; Cell Proliferation; Cell Survival; Fibroblast Growth Factor 2; Membrane Proteins; Mice; Mouse Embryonic Stem Cells; Nerve Growth Factor; Neurons; Oligopeptides; Peptide Fragments; Proline; Recombinant Proteins; Thyrotropin-Releasing Hormone

Short endogenous peptides represent one of the most important constituents of the mammalian body's general regulatory system. Some synthesized analogs and modified natural peptides (eg, corticotropins) also show high biological activity. Nevertheless, the mechanism of action of regulatory peptides remains unclear. To explain the effects of peptides of intermolecular processes, the hypothesis that a synactonal mechanism underlies the action of regulatory peptides, exemplified by the heptapeptide Semax, has been proposed. Thus, in the total pool of Semax metabolites, which includes the cleavage products of the parental molecule, we can distinguish the functional core, represented by the major metabolic products-peptides HFPGP and PGP. These peptides have their own binding sites with similar although differing characteristics. Together with Semax, they constitute a single complex of bioregulators acting in a certain sequence and in interaction, ie, synacton. It can be assumed that the diverse clinically significant effects of the drug Semax are determined by its synacton. Specific interactions between some tritium-labeled peptides (basic constituents of the Semax synacton) and plasma membranes of neurons have been characterized. Only a few peptides of the Semax synacton showed competitive activity for the Semax binding sites. Fragments comprising 5 amino acid residues (EHFPG and HFPGP) showed the highest competitive activity. We also characterized the processes of specific ligand-receptor interactions of some tritium-labeled corticotropins ([

Topics: Adrenocorticotropic Hormone; Animals; Cell Membrane; Male; Neurons; Oligopeptides; Peptide Fragments; Proline; Rats

Brain stroke continues to claim the lives of million people every year. To build the effective strategies for stroke treatment it is necessary to understand the neuroprotective mechanisms that are able to prevent the ischemic injury. Consisting of the ACTH

Topics: Adrenocorticotropic Hormone; Animals; Antigen Presentation; Brain Ischemia; Disease Models, Animal; Gene Expression Profiling; Genes, Immunoglobulin Heavy Chain; Immunoglobulin Heavy Chains; Male; Middle Cerebral Artery; Neuroprotective Agents; Oligopeptides; Peptide Fragments; Proline; Rats; Rats, Wistar; Stress, Physiological; Transcriptome

The influence two original derivatives of a therapeutically important peptide, bearing arachidonic acid residue with semax and proglyprol, upon platelet aggregation have been studied in vitro. It is established that both derivatives, in contrast to the parent peptide, possess moderate anti-aggregant properties and produce a dose-dependent decrease in the interplatelet interaction induced by ADP, epinephrine, and arachidonic acid within the concentration range of 0.018 - 1.8 mM. This activity was more pronounced for arachidonoylsemax in comparison with arachidonoylproglyprol.

Topics: Adenosine Diphosphate; Adrenocorticotropic Hormone; Arachidonic Acid; Blood Platelets; Cells, Cultured; Drug Design; Epinephrine; Humans; Neuroprotective Agents; Oligopeptides; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Proline; Structure-Activity Relationship

The synthetic peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is used successfully in acute stroke therapy. In spite of numerous studies on the subject, many aspects of the neuroprotective effects of the peptide remain unknown. We studied the action of Semax and its C-terminal tripeptide Pro-Gly-Pro on the expression of the VEGF gene family (Vegf-a, Vegf-b, Vegf-c, Vegf-d, and Plgf) and their receptors (Vegfr-1, Vegfr-2, and Vegfr-3) in the frontoparietal cortex region of the rat brain at 3, 24, and 72 h after permanent left middle cerebral artery occlusion (pMCAO). The relative mRNA level of the genes studied was assessed using real-time reverse transcription-PCR. The Vegf-b and Vegf-d genes were most affected by the peptides, which resulted in their most noticeable activation at 3 h after pMCAO. The level of Vegf-d transcripts decreased considerably, whereas the mRNA level of the Vegf-b gene was significantly increased after 72 h of treatment with each of the peptides. In addition, the effects of the peptides on the expression of the Vegf-b and Vegf-d genes were the opposite of the action of ischemia. It is suggested that the identified effects of the peptides diminish the effects of ischemia, thus participating in the positive therapeutic effect of Semax on ischemic stroke.

Topics: Adrenocorticotropic Hormone; Animals; Frontal Lobe; Infarction, Middle Cerebral Artery; Male; Neuroprotective Agents; Oligopeptides; Parietal Lobe; Peptide Fragments; Proline; Rats; Rats, Wistar; Receptors, Vascular Endothelial Growth Factor; RNA, Messenger; Transcription, Genetic; Vascular Endothelial Growth Factor A

The neuropeptide preparation Semax (Met-Glu-His-Phe-Pro-Gly-Pro) has been employed successfully in clinical practice for treating patients with severe brain blood circulation disorders. In spite of numerous studies, many aspects of the therapeutic effects of this preparation remain unknown. In this context, the effects of Semax and its C-end tripeptide PGP on the functional morphology of nervous tissue cells were studied in the normal rat brain and in a model of incomplete global rat brain ischemia. In control animals, both peptides activated the capillary network and caused similar morphological changes to neurons and the neuropil regions. We show here for the first time at the histological level that Semax and PGP increased proliferation of the neuroglia, blood vessel endothelium, and progenitor cells in the subventricular zone. In these experimental conditions, only Semax abated the manifestation of ischemic damage to the nervous tissue. This was probably attributable to a decrease in vascular stasis symptoms as well as the trophic effect of the peptide.

Topics: Adrenocorticotropic Hormone; Animals; Brain; Brain Ischemia; Cell Proliferation; Humans; Male; Neuroprotective Agents; Oligopeptides; Peptide Fragments; Pilot Projects; Proline; Rats; Rats, Wistar

Semax (100 microM) and its Pro-Gly-Pro fragment (20 and 100 microM) delayed the development of calcium dysregulation and reduction of the mitochondrial potential in cultured cerebellar granule cells under conditions of glutamate neurotoxicity. Incubation with these peptides improved neuronal survival by on average 30%. The neuroprotective effect of semax in cerebral ischemia/hypoxia can be due to improvement of mitochondrial resistance to "calcium" stress.

Topics: Adrenocorticotropic Hormone; Animals; Calcium; Cell Survival; Glutamic Acid; Homeostasis; Neurons; Oligopeptides; Peptide Fragments; Proline; Rats; Rats, Wistar

Stress increased secretory activity of mast cells in the mesentery and subcutaneous fat of rats. Intraperitoneal injection of Semax and prolyl-glycyl-proline in doses of 0.05 and 1 mg/kg, respectively, 1 h before stress abolished this effect. The test preparations did not modulate secretory activity of mast cells in unstressed animals. Semax and prolyl-glycyl-proline in vitro prevented activation of mast cells with synacten and acetylcholine. The stabilizing effect of peptides on mast cells probably determines their antiulcer activity.

Topics: Acetylcholine; Adrenocorticotropic Hormone; Animals; Animals, Outbred Strains; Disease Models, Animal; Injections, Intraperitoneal; Male; Mast Cells; Mesentery; Oligopeptides; Peptide Fragments; Proline; Rats; Stress, Psychological

Intranasal administration of Semax, peptide Pro-Gly-Pro, and a mixture of peptides Pro-Gly+Gly-Pro to rats for 5 days enhanced anticoagulant and fibrinolytic potential of the plasma (total fibrinolytic activity and plasmin and plasminogen activator activities) and decreased antiplasmin concentration. Semax and Pro-Gly-Pro decreased the weight of thrombi during experimental thrombosis.

Topics: Adrenocorticotropic Hormone; Animals; Anticoagulants; Blood Coagulation; Dipeptides; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; Male; Oligopeptides; Peptide Fragments; Proline; Rats