A. A. Boldyrev

Protective Effect of Carnosine on Cu,Zn-Superoxide Dismutase during Impaired Oxidative Metabolism in the Brain in Vivo

Natural hydrophilic antioxidant carnosine protects cerebral cytosolic Cu,Zn-superoxide dismutase (SOD) under conditions of oxidative stress in various in vivo models: short-term hypobaric hypoxia in rats and accumulation of age-related changes in senescence-accelerated mice (SAMP). Administration of carnosine preventing Cu,Zn-SOD inactivation reduced mortality in rats and prolonged average life span in SAMP-mice.

Effect of homocysteine and homocysteic acid on glutamate receptors on rat lymphocytes

Homocysteine and homocysteic acid increased the stationary level of reactive oxygen species in rat lymphocytes, homocysteic acid being more potent in this respect. The effect of this compound was realized via ionotropic NMDA receptors and group III metabotropic glutamate receptors. Incubation of lymphocytes with homocysteic acid increased intracellular Ca2+ concentration, activated of protein kinase C, and induced accumulation of reactive oxygen species, which reflected the involvement of homocysteic acid into cell signaling mechanisms.

Expression of NMDA receptors in multipotent stromal cells of human adipose tissue under conditions of retinoic acid-induced differentiation

The system of NMDA glutamate receptors in human adipose tissue multipotent stromal cells and SH-SY5Y human neuroblastoma cells was used as a model for studies of NMDA receptor expression during neurodifferntiation. Glutamate NMDA receptors were detected in multipotent stromal cells of human adipose tissue. The expression of NR1 subunits of NMDA receptors increased significantly after 6-day incubation of multipotent stromal cells of human adipose tissue with 10 µM retinoic acid. Only NR1 subunits of NMDA receptors were expressed in SH-SY5Y neuroblastoma cells. Incubation with retinoic acid did not promote the appearance of mRNA of other subunits (NR2A-D, NR3). The results indicate that expression of NMDA receptors can serve as an indicator of neuronal differentiation of cells and as a marker of the efficiency of neuronal differentiation protocol.

Homocysteinic Acid Causes Oxidative Stress in Lymphocytes by Potentiating Toxic Effect of NMDA

Short-term incubation of lymphocytes with homocysteine or its oxidation product homocysteinic acid increased the formation of reactive oxygen species and cell necrosis (in case of homocysteinic acid). Effective concentration of homocysteine and homocysteinic acid (500 µM) significantly surpassed the level observed during hyperhomocysteinemia. The addition of homocysteinic acid in a nontoxic concentration of 100 µM potentiated the toxic effect of NMDA and led to massive cell death. During hyperhomocysteinemia the amount of these metabolites in the blood was much higher than in the brain. Oxidative stress produced by these substances can result from activation of NMDA glutamate receptors that were recently detected on lymphocytes.

Peculiarities of Carnosine Metabolism in a Patient with Pronounced Homocarnosinemia

The article describes a case of homocarnosinemia with increased liquor and plasma content of homocarnosine, increased urinary excretion of homocarnosine, and low activity of serum carnosinase. These metabolic disturbances were accompanied by moderate neurological disorders. Changes in carnosine metabolism in family members were less pronounced and not accompanied by neuropathological symptoms.

Laser Modification of the Blood in Vitro and in Vivo in Patients with Parkinson's Disease

The effect of He-Ne laser radiation on activity of MAO B, Cu/Zn-SOD, Mn-SOD, and catalase in blood cells from patients with Parkinsons disease was studied in vivo and in vitro. The effects of intravenous in vivo irradiation (intravenous laser therapy) were more pronounced than those observed in similar in vitro experiments. It is concluded that generalized effect of laser therapy involves interaction between blood cells.

Effect of Carnosine and Related Compounds on Proliferation of Cultured Rat Pheochromocytoma PC-12 Cells

The study was undertaken to determine the mechanism of carnosine effect on cell proliferation. We studied the effect of carnosine and its derivatives on cell cycle progression in cultured rat pheochromocytoma cells (PC-12). It was found that 48-h incubation of PC-12 cells with carnosine in concentrations of 10-50 mM led to deceleration of cell proliferation, reduction of G0/G1 peak, and accumulation of S- and G2/M-phase cells. Methylation of the carnosine molecule by 1N-position of the imidazole ring potentiated its effect on cell proliferation. Acetylation of the carnosine molecule by free β-amino group attenuated its effect.

Effects of Carnosine on Polyamine Levels in Red Blood Cells of Patients with Hypertonic Discirculatory Encephalopathy

The levels of polyamines (putrescine, spermine, spermidine) in erythrocytes from patients with hypertonic discirculatory encephalopathy are reduced (by 37, 45, and 50%, respectively) in comparison with the corresponding parameters in the control group. Addition of carnosine to the treatment protocol for chronic brain ischemia normalized the content of putrescine and spermine. The mechanisms of carnosine influence on polyamine metabolism are discussed: trapping of acrolein, end-product of polyamine oxidation, and compensation of NMDAreceptor excitotoxicity.

Carnosine and related compounds inhibit chemiluminescence of human plasma lipoproteinsin vitro

The antioxidant activity of carnosine and related compounds (5 and 10 mM) is assessed from the chemiluminescence curve using a model of Fe-initiated lipid peroxidation of human serum apoB-lipoproteins. These agents lower to different degrees the amplitudes of “fast” and “slow” bursts, the reaction rate, and the chemiluminescence light sum; the latency is prolonged, which may occur upon reduction of lipid hydroperoxides and/or inactivation of free radicals.

Role of superoxide dismutase in the pathogenesis of amyotrophic lateral sclerosis

Activity of cytosolic Cu2+/Zn2+-superoxide dismutase and total superoxide dismutase activity of the spinal fluid of patients with sporadic amyotrophic lateral sclerosis were measured. These parameters correlates with the form of this disease, its duration, and the severity of neurological disorders. Our findings indicate that free-radical processes are involved in the damage to motor neurons in this disease.