Search

Depletion of glucose/glutamine is associated with a reduced level of Nicotinamide Adenine Dinucleotide Phosphate (NADPH), which is an important cofactor for replenishing cellular glutathione. Accordingly, starvation leads to increased levels of reactive oxygen species (ROS). For decreasing the ROS, cells activate detoxifying machinery based on the action of transcription factor Nuclear Factor Erythroid 2 Like 2 (NRF2). One of the NRF2 targets is an antioxidative enzyme, NAD(P)H: Quinone Dehydrogenase 1 (NQO1), which has a binding site for NRF2 in its promoter. The NRF2-NQO1 axis was explored in three head and neck-originating cancer cell lines: Cal 27, Detroit 562 and FaDu and in immortalized fetal lung fibroblasts: IMR-90 Four nutritional conditions were applied for 48 hours:a)NC1: high glucose (4, 5 g/L) + glutamine (0, 584 g/L) ; b)NC2: low glucose (1 g/L) + glutamine (0, 584 g/L) ; c)NC3: traces of glucose and glutamine provided by fetal bovine serum (FBS ; 0.69 mM glucose ; 0.05 mM glutamine) ; d)NC4: traces of glucose + glutamine (0, 584 g/L). Cellular viability, proliferation and ROS were measured. Quantification of NRF2 and NQO1 transcripts was combined with chromatin immunoprecipitation (ChIP) for discovering H3K27me3 enrichment and the amount of NRF2 bound to NQO1 promoter. Among the three cancer cell lines, FaDu was the most dependent on glucose for maintaining proliferation and glutamine had a minimal effect on restoring FaDu replicative potential. IMR-90 cells were entirely dependent on glucose. NRF2- NQO1 axis response to nutritional stress was cell type specific. Cal 27, Detroit 562 and IMR-90 upregulated NQO1 transcription under the NC3 condition.e There was no significant change in the NQO1 transcription rate in FaDu. ChIP analyses revealed that NC3 influences the amount of H3K27me3 ( a 3.50 and 1.25-fold increase in Cal 27 and FaDu, respectively) and NRF2 a(3-fold increase in Cal 27, 33-fold decrease in FaDu), bound to the NQO1 promoter.

Oxidative stress, capable of eliciting damage to various biomolecules including DNA, is a recognized component of diabetes mellitus and its complications. Metabolic syndrome (MetS) is associated with the development of type 2 diabetes mellitus (T2DM), as well as other unfavorable outcomes. The aim of this study was to elucidate the role of oxidative stress in the development of T2DM, by investigating association of oxidative DNA damage with metabolic parameters in subjects with MetS and early T2DM.Selected anthropometric and biochemical parameters of MetS, inflammation and oxidative DNA damage: body mass index (BMI), fatty liver index (FLI), waist circumference (WC), total cholesterol, HDL and LDL-cholesterol, GGT, uric acid, total leukocyte/neutrophil count, and urinary 8-oxo-deoxyguanosine (u-8-oxodG) were assessed in male subjects with MetS and both younger (≤55 years) and older (>55 years) subjects with T2DM of short duration without complications.BMI, FLI, WC, total and LDL-cholesterol and uric acid were higher, while the u-8-oxodG was lower in MetS group, when compared to older T2DM subjects. None of these parameters were different neither between MetS and younger T2DM, nor between two sub-groups of subjects with T2DM. Values of CRP, HDL-cholesterol, triglycerides, GGT, leukocytes and neutrophils were not different between all examined groups of subjects. Age-dependent increase in u-8-oxodG suggests that aging process, rather than metabolic disturbances or diabetes per se plays a pivotal role in development of oxidative DNA-damage in T2DM. Oxidative DNA damage cannot serve as an universal early marker of T2DM.

The results point out that the hydrophobic moment measurements provide simple and fast description of complex protein structures, with a perspective of being used in virtual screening of de novo proteins.

Cilj ovog istraživanja je ispitati koncentracije vitamina D u serumu u djece sa zloćudnom bolešću.

Binary and ternary coding patterns of the amino acid polarity play an important role in analysis and design of peptide and protein structures. Recent investigations made by different authors suggest that de novo proteins constructed using specific patterns of amino acid polarity could be used for different applications in science and nanotechnology. This paper presents a new rule-based system for the structural characterization and construction of de novo proteins, based on the ternary patterns of sequence polarity, i.e., polar amino acids (H, Q, N, K, D, E, R), neutral amino acids (S, P, T, W, G, Y), and nonpolar amino acids (F, L, I, M, V, A, C). The extracted rules may help to predict and design different supersecondary protein structures with high probability. Audification of the protein and gene sequences is discussed as a possible alternative/complementary method for the secondary and supersecondary structure analysis and design.

The results of Biro, Blalock, Root-Bernstein and Siemion showed that peptides specified by the complementary DNA and RNA sequences, i.e., sense and antisense peptides, interact with increased probability. In this study we show that the residue contact energies calculated by the Miyazawa-Jernigan contact potential model support the recognition rules of peptide-peptide interaction based on the complementary coding of DNA and RNA sequences in 3'→5' and 5'→3' directions. The properties of the complementary coding patterns of sense-antisense peptide pairs are closely related to structural diversity, functional specificity and the evolutionary impact of protein and peptide ligand-receptor interactions.

Introduction: Statins have been shown to possess antioxidant effects and our previous results showed that simvastatin significantly decrease malondialdehyde (MDA) levels in plasma and tissue of rats. Here we wanted to investigate the influence of rosuvastatin (ROSU) on MDA level and superoxide dismutase (SOD) activity in plasma and liver of rats, both considered to be markers of oxidative stress. Material and Methods: Thirty-six male Wistar rats were divided in one control group (saline) and two experimental groups (ROSU 5 mg/kg/day and 10 mg/kg/day). Drug and saline were given orally for period of 3 weeks. Animals were sacrificed with ether 24 hours after last dose. Blood samples were obtained directly from heart and liver tissue was rinsed with saline. MDA in plasma was measured with high performance liquid chromatography using commercially HPLC kits, while in liver using Drury method. SOD activity was measured in plasma with sensitive spectrophotometric assay and in liver using Flohé and Ötting method. Data were analyzed using ANOVA test. Results are expressed as the means and SDs. Results: ROSU in both doses decreased MDA level in liver but decrease was significant (p

There are diverse experimental data about the influence of gemfibrozil (GEM) on the production of hydrogen per- oxide (H2O2) and antioxidant enzymes. We investigated the influence of GEM treatment on the production of malondialde- hyde (MDA) level in tissues of normolipidaemic Wistar and Fisher rats which is an index of lipid peroxidation. Because serum paraoxonase 1 (PON1) is an important enzyme with specific protective function on metabolism of lipid peroxides, we examined the influence of GEM on PON1 activity in liver and serum. MDA level and enzyme activities were also determined 10 days after withdrawal of GEM treatment. The significantly increased levels of MDA in liver, kidney and heart of both rat strains were obtained after 3 weeks of GEM treatment. We propose two possibilities for the increase of MDA levels caused by GEM, induction of peroxisome proliferation and activities of enzymes that participated in occurrence of H2O2 and possible reduction of enzyme activities including in H2O2 metabolism. Ten days after withdrawal of GEM treatment, MDA levels in all tissue levels of both rat strains were less in comparison with GEM treatment. GEM caused a significant drop of PON1 activity in serum and liver of Fisher rats, and in liver of Wistar rats. We suggest that GEM, through induction of lipid peroxi- dation, caused the damage of hepatocytes with consequent reduction of PON1 synthesis. The increase in PON1 activity in serum and tissues of both rat strains 10 days after withdrawal of GEM treatment shows the fast recovery of enzyme synthesis.