Marzena Gutowicz

Publications of Marzena Gutowicz

• [Intracellular transport proteins: classification, structure and function of kinesins].

  Authors: Agnieszka Chudy, Beata Gajewska, Marzena Gutowicz, Anna Barańczyk-Kuźma

  Postȩpy higieny i medycyny doświadczalnej (Online). 01/2011; 65:588-96.

  Correct cell functioning, division and morphogenesis rely on efficient intracellular transport. Apart from dyneins and myosins, kinesins are the main proteins responsible for intracellular movement.Correct cell functioning, division and morphogenesis rely on efficient intracellular transport. Apart from dyneins and myosins, kinesins are the main proteins responsible for intracellular movement. Kinesins are a large, diverse group of motor proteins, which based on phylogenetic similarity were classified into fourteen families. Among these families, due to the location of their motor domains, three groups have been characterized: N-, C- and M-kinesin. As molecular motors, kinesins transport various molecules and vesicles mainly towards the microtubule plus end (from the cell body) participating in anterograde transport, although there are also kinesins involved in retrograde transport (C-kinesins). Kinesins are also involved in spindle formation, chromosome segregation, and spermatogenesis. Because of their great importance for the correct functioning of cells, mutations in kinesin coding genes may lead to such neurodegenerative diseases as dominant hereditary spastic paraplegia or Charcot-Marie-Tooth disease.

• [The influence of reactive oxygen species on the central nervous system].

  Authors: Marzena Gutowicz

  Postȩpy higieny i medycyny doświadczalnej (Online). 01/2011; 65:104-13.

  Oxidative stress can be defined as a rise of oxidative potential or decrease of antioxidant status. Oxidative stress is caused by reactive oxygen species (ROS) which are produced by one-electronOxidative stress can be defined as a rise of oxidative potential or decrease of antioxidant status. Oxidative stress is caused by reactive oxygen species (ROS) which are produced by one-electron reduction of oxygen in the electron transport chain, as well as many other reactions. Effects of ROS can result in cellular membrane damage, structural and functional changes in enzymatic and non-enzymatic proteins, and damage to the DNA structure. Excessive generation of free radicals, decrease of enzymatic antioxidant activity, and/or reducing agents are considered as the main causes of oxidative stress. Since the brain contains a large amount of polyunsaturated fatty acids, consumes up to 20% of oxygen used by the whole body, and shows low antioxidant activity, it seems to be especially vulnerable to oxidative stress. Numerous data show the significant role of oxidative stress in pathogenesis of many neurodegenerative diseases.

• The influence of heroin abuse on glutathione-dependent enzymes in human brain.

  Authors: Marzena Gutowicz, Beata Kaźmierczak, Anna Barańczyk-Kuźma

  Drug and alcohol dependence. 01/2011; 113(1):8-12.

  Heroin is an illicit narcotic abused by millions of people worldwide. In our earlier studies we have shown that heroin intoxication changes the antioxidant status in human brain. In the present workHeroin is an illicit narcotic abused by millions of people worldwide. In our earlier studies we have shown that heroin intoxication changes the antioxidant status in human brain. In the present work we continued our studies by estimating the effect of heroin abuse on reduced glutathione (GSH) and enzymes related to this cofactor, such as glutathione S-transferase detoxifying electrophilics (GST) and organic peroxides (as Se-independent glutathione peroxidase-GSHPx), and Se-dependent glutathione peroxidase (Se-GSHPx) specific mainly for hydrogen peroxide. Studies were conducted on human brains obtained from autopsy of 9 heroin abusers and 8 controls. The level of GSH and the activity of glutathione-related enzymes were determined spectrophotometrically. The expression of GST pi on mRNA and protein level was studied by RT-PCR and Western blotting, respectively. The results indicated significant increase of GST and GSHPx activities, unchanged Se-GSHPx activity, and decreased level of GSH in frontal, temporal, parietal and occipital cortex, brain stem, hippocampus, and white matter of heroin abusers. GST pi expression was increased on both mRNA and protein levels, however the increase was lower in brain stem than in other regions. Heroin affects all regions of human brain, and especially brain stem. Its intoxication leads to an increase of organic rather then inorganic peroxides in various brain regions. Glutathione S-transferase plays an important role during heroin intoxication, however its protective effect is lower in brain stem than in brain cortex or hippocampus.

• Antioxidant status in different regions of heroin addicts' brain.

  Authors: Marzena Gutowicz, Bożenna Sadurska, Małgorzata Chołojczyk, Maria Pokorska-Lis, Agnieszka Siwińska-Ziółkowska, Anna Barańczyk-Kuźma

  Environmental toxicology and pharmacology. 01/2006; 21(1):80-5.

  Heroin is an illicit narcotic abused by millions of people worldwide. In the present work, we estimated peroxyl radical-trapping capacity (PRTC), oxidative stress markers - malondialdehyde andHeroin is an illicit narcotic abused by millions of people worldwide. In the present work, we estimated peroxyl radical-trapping capacity (PRTC), oxidative stress markers - malondialdehyde and protein carbonyl groups, as well as antioxidant enzymes - superoxide dismutase and catalase, in different regions of brain. Studies conducted on nine brains from heroin abusers and eight from control subjects revealed a decrease in PRTC in each part of heroin intoxicated brains and an increase in lipid peroxidation in brain cortex, brain stem and white matter but not in hippocampus. Protein oxidation was increased in hippocampus and in brain stem, but it was unchanged in gray and white matters. Superoxide dismutase and catalase activities were unchanged in heroin addicts. We conclude that heroin intoxication changes the antioxidant status in human brain by increasing the amount of organic rather then inorganic peroxides. The most severe condition of oxidative stress occur in brain stem.

• Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain.

  Authors: Anna Barańczyk-Kuźma, Magdalena Kuźma, Marzena Gutowicz, Beata Kaźmierczak, Jacek Sawicki

  Acta biochimica Polonica. 02/2004; 51(1):207-12.

  GST pi, the main glutathione S-transferase isoform present in the human brain, was isolated from various regions of the brain and the in vitro effect of tricyclic antidepressants on its activity wasGST pi, the main glutathione S-transferase isoform present in the human brain, was isolated from various regions of the brain and the in vitro effect of tricyclic antidepressants on its activity was studied. The results indicated that amitripyline and doxepin - derivatives of dibenzcycloheptadiene, as well as imipramine and clomipramine - derivatives of dibenzazepine, inhibit the activity of GST pi from frontal and parietal cortex, hippocampus and brain stem. All these tricyclics are noncompetitive inhibitors of the enzyme with respect to reduced glutathione and noncompetitive (amitripyline, doxepin) or uncompetitive (imipramine, clomipramine) with respect to the electrophilic substrate. Their inhibitory effect is reversible and it depends on the chemical structure of the tricyclic antidepressants rather than on the brain localization of the enzyme. We conclude that the interaction between GST pi and the drugs may reduce their availability in the brain and thus affect their therapeutic activity. On the other hand, tricyclic antidepressants may decrease the efficiency of the enzymatic barrier formed by GST and increase the exposure of brain to toxic electrophiles. Reactive electrophiles not inactivated by GST may contribute in adverse effects caused by these drugs.

• Antioxidant status in different regions of heroin addicts’ brain

  Authors: Marzena Gutowicz, Bożenna Sadurska, Małgorzata Chołojczyk, Maria Pokorska-Lis, Agnieszka Siwińska-Ziółkowska, Anna Barańczyk-Kuźma

  Environmental Toxicology and Pharmacology.

  Heroin is an illicit narcotic abused by millions of people worldwide. In the present work, we estimated peroxyl radical-trapping capacity (PRTC), oxidative stress markers – malondialdehyde andHeroin is an illicit narcotic abused by millions of people worldwide. In the present work, we estimated peroxyl radical-trapping capacity (PRTC), oxidative stress markers – malondialdehyde and protein carbonyl groups, as well as antioxidant enzymes – superoxide dismutase and catalase, in different regions of brain. Studies conducted on nine brains from heroin abusers and eight from control subjects revealed a decrease in PRTC in each part of heroin intoxicated brains and an increase in lipid peroxidation in brain cortex, brain stem and white matter but not in hippocampus. Protein oxidation was increased in hippocampus and in brain stem, but it was unchanged in gray and white matters. Superoxide dismutase and catalase activities were unchanged in heroin addicts.We conclude that heroin intoxication changes the antioxidant status in human brain by increasing the amount of organic rather then inorganic peroxides. The most severe condition of oxidative stress occur in brain stem.

• The analysis of selected neurotransmitter concentrations in serum of patients with Tourette syndrome.

  Authors: Piotr Janik, Anna Kalbarczyk, Marzena Gutowicz, Anna Barańczyk-Kuźma, Hubert Kwieciński

  Neurologia i neurochirurgia polska. 44(3):251-9.

  Metabolic disturbances of excitatory and inhibitory neurotransmitters are implicated in pathogenesis of Tourette syndrome (TS). The aim of the study was to measure serum concentrations of glutamicMetabolic disturbances of excitatory and inhibitory neurotransmitters are implicated in pathogenesis of Tourette syndrome (TS). The aim of the study was to measure serum concentrations of glutamic acid, g-aminobutyric acid (GABA) and glycine in TS patients and evaluate any correlation between neurotransmitter levels and age at onset, actual age, gender, tic severity, duration of the disease and concomitant psychiatric disorders. Sixty-seven TS patients, aged 16-59, and 57 healthy controls, aged 19-37, were enrolled in the study. Information regarding medical history and physical investigation was collected using a short questionnaire. Sixty-seven percent of patients were medication-free at the time of examination and the rest had withheld treatment for 24 hours before. Blood samples were taken after a 12-hour fasting period. HPLC technique was used. The TS group had higher glutamic acid and lower GABA levels. Glycine concentrations were comparable. No differences regarding neurotransmitter concentrations between treated and non-treated patients were found. Patients with concomitant obsessive-compulsive disorder and severe tics had higher glutamate levels. Glutamate concentrations correlated positively with the number of comorbid psychiatric disorders and GABA concentrations correlated negatively with the number of behavioural problems in patients with comorbidities. There was no correlation between analysed neurochemicals and age, gender, age at onset or disease duration. Imbalance between excitatory and inhibitory systems in the brains of TS patients may be reflected by glutamate and GABA serum level changes. Glutamate and GABA may be biomarkers of the disease and high concentration of glutamate may indicate more severe course of TS.