prolyl-glycyl-proline and glycylproline

The family of regulatory proline-containing peptides (PCPs), also known as glyprolines, exhibit significant biological activity. The group of glyprolines includes Gly-Pro (GP), Pro-Gly-Pro (PGP), cyclic Gly-Pro (cGP), as well as PGP derivatives, for example, N-acetylated PGP (N-a-PGP) and N-methylated PGP (N-m-PGP). PCPs are engaged in various biological processes including the proinflammatory neutrophil chemoattraction in lung diseases, inflammatory bowel diseases or ischemic stroke. Glyprolines have been also postulated to play an important role as atheroprotective and anticoagulant agents, exhibit neuroprotective effects in Parkinson's disease, as well as regulate insulin-like growth factor (IGF) homeostasis. It was also noticed that PCPs inhibit proliferation and migration of keratinocytes in wound healing, protection of the gastric mucosa and stimulation of its regeneration. The regulatory glyprolines are derived from endogenous and exogenous sources. Most PCPs are derived from collagen or diet protein degradation. Recently, great interest is concentrated on short proline-rich oligopeptides derived from IGF-1 degradation. The mechanism of PCPs biological activity is not fully explained. It involves receptor-mediated mechanisms, for example, N-a-PGP acts as CXCR1/2 receptor ligand, whereas cGP regulates IGF-1 bioavailability by modifying the IGF-1 binding to the IGF-1 binding protein-3. PGP has been observed to interact with collagen-specific receptors. The data suggest a promising role of PGP as a target of various diseases therapy. This review is focused on the effect of PCPs on metabolic processes in different tissues and the molecular mechanism of their action as an approach to pharmacotherapy of PCPs-dependent diseases.

Topics: Dipeptides; Gastric Mucosa; Humans; Inflammatory Bowel Diseases; Neutrophils; Oligopeptides; Peptides; Peptides, Cyclic; Proline; Signal Transduction; Stroke; Wound Healing

Our own data and data from the literature on the regulatory role of the simplest proline-containing peptides GP, PG, PGP, GPGG, and cyclic-PG are summarized. These peptides are involved in homeostasis of gastric mucosa and the anticoagulant and fibrinolytic potential of blood plasma. They also potentiate memory consolidation processes in the central nervous system. The most probable sources of these peptides are polypeptide precursors of collagen, elastin, and enterostatin.

Topics: Animals; Blood Coagulation; Dipeptides; Fibrinolysis; Gastric Mucosa; Homeostasis; Humans; Memory; Oligopeptides; Proline

Topics: Administration, Intranasal; Administration, Intravenous; Animals; Area Under Curve; Blood; Blood Chemical Analysis; Brain; Central Nervous System Agents; Dipeptides; Male; Oligopeptides; Proline; Proteolysis; Rats, Wistar; Time Factors

Pro-Gly-Pro and its metabolite Gly-Pro effectively prevented the development of erosive and ulcerative lesions of the gastric mucosa in rats under conditions of water-immersion restraint stress by restoring the oxidatant-antioxidant balance in the total fraction of gastric mucosa cells. Pro-Gly was least effective in this respect. We conclude that glyprolines hold much promise as pharmaceutical products, which can be used in gastroenterological practice for the prevention and therapy of ulcer disease of the stomach and duodenum.

Topics: Animals; Dipeptides; Gastric Mucosa; Homeostasis; Male; Oligopeptides; Proline; Rats; Rats, Wistar; Statistics, Nonparametric; Stomach Ulcer; Stress, Physiological

Experiments on outbred albino male rats showed that psychoemotional stress induced by intraperitoneal injection of cholecystokinin-4 (100 microg/kg) increased anxiety, impaired orientation and exploration activities in the elevated plus-maze and hole-board tests, and increased the level of depression of Porsolt test. Preliminary intranasal administration of glyprolines (15 min before cholecystokinin) in a dose of 3.7 micromol/kg prevented the development of stress-induced behavioral disturbances. Administration of peptides 30 min after cholecystokinin-4, i.e., to rats with developed behavioral disturbances, almost completely abolished these disturbances.

Topics: Animals; Anxiety; Behavior, Animal; Depression; Dipeptides; Exploratory Behavior; Male; Maze Learning; Oligopeptides; Proline; Rats; Stress, Psychological; Tetragastrin

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

Intraperitoneal administration of the PGP did not change basal mucosal blood flow, whereas the PG and GP significantly decreased it. Ethanol and Indomethacin caused a rapid and stable decrease in the blood flow. Administration of the PGP prior to ethanol abolished this effect. Injections of the PGP and PG following Indomethacin administration prevented reduction of the mucosal blood flow. Administration of the GP did not change the blood flow decrease induced with Indomethacin. The mucosal blood flow correction seems to be one of the possible mechanisms of the PGP and PG antiulcer effect. The effect seems to be realised through a change in the CNS activity.

Topics: Animals; Anti-Ulcer Agents; Dipeptides; Ethanol; Gastric Mucosa; Indomethacin; Male; Oligopeptides; Proline; Rats; Regional Blood Flow