L. A. Andreeva

Effects of semax and its Pro-Gly-Pro fragment on calcium homeostasis of neurons and their survival under conditions of glutamate toxicity

Semax (100 µM) and its Pro-Gly-Pro fragment (20 and 100 µM) 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.

Structural-functional study of glycine-and-proline-containing peptides (Glyprolines) as potential neuroprotectors

A synthetic scheme for preparation of (Gly-Pro)n, (Pro-Gly)n (n = 2, 3), and (Pro-Gly-Pro)n (n = 1, 2) peptides was elaborated. The effect of the synthesized peptides and the Gly-Pro and Pro-Gly dipeptides on survival of cultured cells of PC12 rat pheochromocytoma was studied under the conditions of oxidative stress induced by brief incubation of the cells with hydrogen peroxide. Peptides of the general formula (Gly-Pro)n and the Pro-Gly-Pro peptide at a concentration of 0.2–100 μM were shown to decrease the number of damaged cells. The Gly-Pro peptide was the most active and decreased the number of damaged cells by 49% on average at a concentration of 100 μM.

The neuroprotective effects of Semax in conditions of MPTP-induced lesions of the brain dopaminergic system.

This report describes studies of the effects of the ACTH(4–10) analog Semax (MEHFPGP) on the behavior of white rats with lesions to the brain dopaminergic system induced by the neurotoxin MPTP. Neurotoxin was given as single i.p. doses of 25 mg/kg. Neurotoxin injections were shown to decrease movement activity and increase anxiety in the animals. Daily intranasal administration of Semax at a dose of 0.2 mg/kg decreased the severity of MPTP-induced behavioral disturbances. The protective activity of Semax in MPTP-induced lesions of the brain dopaminergic system may be associated with both its modulating effect on the dopaminergic system and the neurotrophic action of the peptide.

The combined antidiabetogenic and anticoagulation effecta of tripeptide Gly-Pro-Arg as estimated in the model of persistent hyperglycemia in rats

135 It was shown earlier that the regulatory peptides Pro–Gly, Pro–Gly–Pro [1], Phe–Pro–Gly–Pro [1⎯4], Pro–Gly–Pro–Leu [5], Pro–Gly–Pro–Arg, Pro–Gly–Arg [6] have both protective and therapeu tic effects on the development of insulin dependent alloxan diabetes mellitus (IDDM). During IDDM development the functional activity of the anticoagu lative system (AS) is depressed, and this frequently causes blood clotting. The suppression of the AS func tion in IDDM is typical of both humans [7] and ani mals [4].

Effect of Glyprolines PGP, GP, and PG on Homeostasis of Gastric Mucosa in Rats with Experimental Ethanol-Induced Gastric Ulcers

The decrease in the severity of erosions and ulcer lesions after preventive treatment with PGP or PG correlated with a decrease in the content of lipid peroxidation products to a control level. Activities of SOD and catalase also returned to control values. GP produced the weakest effect on pro- and antioxidant state of the gastric mucosa. We concluded that the pronounced preventive effect of PGP and PG on the development of ethanol-induced erosions and ulcer lesions is largely determined by their antioxidant properties. Glyprolines can be considered as a promising means for prevention and treatment of stomach and duodenal ulcers.

Effect of the PRO-GLY-PRO peptide on hemostasis and lipid metabolism in rats with hypercholesterolemia

333 It is known that excess cholesterol consumed with food may induce atherosclerosis and atherothrombo sis [1, 2]. Accumulation of cholesterol on injured walls of blood vessels induces subsequent formation of atheromatous plaques [3]. Atherosclerotic process in blood vessels is caused by alteration of the lipid profile by activating lipid peroxidation; an increase in the blood level of low density lipoprotein cholesterol (LDL CS) is the main factor inducing pathologic changes in vessels [1]. Damage of endothelium by oxi dized LDL CS impairs its ability to produce endoge nous vasodilator substances; therefore, vessels in the area of lesion are prone to vasospasm, in particular, vasospasm of coronary arteries. Thus, search for anti lipidemic drugs is of importance. Since atherothrom bosis is an important symptom of lipid metabolism disorder in the human body, antithrombotic therapy is used together with recovery of lipid metabolism and other procedures [5]. Some amino acids, such as pro line, are known to prevent accumulation of preathero genic LDL CS on artery walls, decrease the risk of atherothrombosis, diabetes mellitus, and atheroscle rosis [6, 7]. Regulatory peptides of the glyproline fam ily (Pro–Gly–Pro, Pro–Gly, and others) have been found to maintain anticoagulant and endocrine func tion in the body [8, 9].

The Modern Concept of the Regulatory Role of Peptides of the Glyproline Family in the Correction of Hemostasis System Function during Development of Diabetes Mellitus

The experimental data on the therapeutic and prophylactic antidiabetogenic effect of di-, tri-, and tetrapeptides of the glyproline family with the additional inclusion of arginine or leucine at different positions are presented. The results are obtained using two animal models: with insulin-dependent diabetes mellitus (type 1), and persistent hyperglycemia similar to development of non-insulin-dependent diabetes mellitus (type 2) in humans. It is shown that repeated intranasal administration of Pro-Gly, Pro-Gly-Pro, Pro-Gly-Pro-Arg, Pro-Gly-Arg, Arg-Pro-Gly, Arg-Pro-Gly-Pro, Gly-Pro-Arg, Pro-Arg-Gly, Pro-Gly-Pro-Leu, Leu-Pro-Gly-Pro peptides to rats with hyperglycemia of different etiology led to the combined normoglycemic and anticoagulant effects in the blood plasma. The concept of the regulatory role of short proline-containing peptides, involving the universality of their action in the organism and directed towards the regulation of both hemostasis and insular systems in a variety of their physiological and clinical manifestations, was formulated.

Antiviral properties of structural fragments of the peptide Selank.

79 Widening of the spectrum of antiviral drugs remains an urgent task. Until now, viral diseases, including influenza, herpes, cytomegaloviral infec� tion, and others, are widespread and poorly controlled infections. Therefore, development of new safe antivi� ral drugs is very important. Peptides constitute one of the most promising classes of physiologically active substances and less studied candidates for creation of these drugs. Peptides have practically no negative side effects because they are endogenous substances. Thus, development of new antiviral drugs on the basis of peptides is an urgent and socially important task. One of the main problems with the use of natural endogenous peptides for drug development is their multiple functions. We previously reported on the pos� sibility to isolate, from a polyfunctional peptide, a

Effect of Glyprolines on Homeostasis of Gastric Mucosa in Rats with Stress Ulcers

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.

Fibrinolytic and hypoglycemic effects of the Pro-Gly-Pro-Leu peptide during development of insulin-dependent diabetes in rats

Repeated (over 7 days) intranasal introduction of the Pro-Gly-Pro-Leu peptide into animals at a dose of 1 mg/kg before injection of the diabetogenic metabolite alloxan provided effective protection of an organism against development of insulin-dependent diabetes mellitus and prevented development of hyper-coagulating alterations in the system of hemostasis. An increasing in the anticoagulating and fibrinolytic activities in rat blood plasma was detected. The peptide under study also showed antidiabetogenic action: repeated intranasal introduction of the Pro-Gly-Pro-Leu peptide into animals for 7 days inhibited development of diabetes symptoms in rats pretreated with alloxan.