An Intergenic rs9275596 Polymorphism on Chr. 6p21 Is Associated with Multiple Sclerosis in Latvians.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, leading to demyelination of neurons and potentially debilitating physical and mental symptoms. The disease is more prevalent in women than in men. The major histocompatibility complex (MHC) region has been identified as a major genetic determinant for autoimmune diseases, and its role in some neurological disorders including MS was evaluated.

Tight DNA-protein complexes isolated from barley seedlings are rich in potential guanine quadruplex sequences.

Background: The concept of chromatin domains attached to the nuclear matrix is being revisited, with nucleus described as a set of topologically associating domains. The significance of the tightly bound to DNA proteins (TBP), a protein group that remains attached to DNA after its deproteinization should be also revisited, as the existence of these interactions is in good agreement with the concept of the topologically associating domain. The work aimed to characterize the DNA component of TBP isolated from barley seedlings.

Modifications of expression of genes and proteins involved in DNA repair and nitric oxide metabolism by carbatonides [disodium-2,6-dimethyl-1,4-dihydropyridine- 3,5-bis(carbonyloxyacetate) derivatives] in intact and diabetic rats.

Studies on the pathogenesis of diabetes mellitus complications indicate that the compounds reducing free radicals and enhancing DNA repair could be prospective as possible remedies. Carbatonides, the disodium-2,6-dimethyl-1,4- dihydropyridine-3,5-bis(carbonyloxyacetate) derivatives, were tested for these properties. EPR spectroscopy showed that metcarbatone was an effective scavenger of hydroxyl radicals produced in the Fenton reaction, etcarbatone, and propcarbatone were less effective, styrylcarbatone was ineffective.

Effects of an Antimutagenic 1,4-Dihydropyridine AV-153 on Expression of Nitric Oxide Synthases and DNA Repair-related Enzymes and Genes in Kidneys of Rats with a Streptozotocin Model of Diabetes Mellitus.

Development of complications of diabetes mellitus (DM), including diabetic nephropathy, is a complex multi-stage process, dependent on many factors including the modification of nitric oxide (NO) production and an impaired DNA repair. The goal of this work was to study in vivo effects of 1,4-dihydropyridine AV-153, known as antimutagen and DNA binder, on the expression of several genes and proteins involved in NO metabolism and DNA repair in the kidneys of rats with a streptozotocin (STZ)-induced model of DM. Transcription intensity was monitored by means of real-time RT-PCR and the expression of proteins by immunohistochemistry.

New 1,4-Dihydropyridines Down-regulate Nitric Oxide in Animals with Streptozotocin-induced Diabetes Mellitus and Protect Deoxyribonucleic Acid against Peroxynitrite Action.

Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic actions of nitric oxide (NO) are responsible to a large extent for development of complications of DM. Search for compounds regulating NO production in patients with DM is thus important for the development of pharmacological drugs.

Genetic variations in the PSMA3, PSMA6 and PSMC6 genes are associated with type 1 diabetes in Latvians and with expression level of number of UPS-related and T1DM-susceptible genes in HapMap individuals.

The ubiquitin-proteasome system (UPS), a key player of proteostasis network in the body, was implicated in type 1 diabetes mellitus (T1DM) pathogenesis. Polymorphisms in genes encoding proteasome subunits may potentially affect system efficiency. However, data in this field are still limited.

1,4-Dihydropyridine derivatives without Ca2+-antagonist activity up-regulate Psma6 mRNA expression in kidneys of intact and diabetic rats.

Impaired degradation of proteins by the ubiquitin-proteasome system (UPS) is observed in numerous pathologies including diabetes mellitus (DM) and its complications. Dysregulation of proteasomal degradation might be because of altered expression of genes and proteins involved in the UPS. The search for novel compounds able to normalize expression of the UPS appears to be a topical problem.

Changes in glucose transporter expression and nitric oxide production are associated with liver injury in diabetes.

In diabetes mellitus (DM), both hyperglycaemia and hyperlipidaemia can initiate accumulation of fat in the liver, which might be further mediated by inducible nitric oxide synthase. We have studied changes in GLUT1, nitric oxide (NO(·)) concentration and liver damage in two rat DM models. STZ model was induced by strepozotocin 50 mg/kg.

PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) genetic diversity in Latvians, Lithuanians and Taiwanese.

PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) genetic diversity was investigated in 1438 unrelated subjects from Latvia, Lithuania and Taiwan. In general, polymorphism of each individual locus showed tendencies similar to determined previously in HapMap populations. Main differences concern Taiwanese and include presence of rs2277460 rare allele A not found before in Asians and absence of rs2295827 rare alleles homozygotes TT observed in all other human populations.

Evaluation of proteasomal gene polymorphisms in Lithuanian patients with asthma.

Objective: To investigate polymorphisms of proteasomal genes PSMA6 (rs1048990 and rs2277460), PSMC6 (rs2295826 and rs2295827) and PSMA3 (rs2348071) in Lithuanian patients with asthma.

Methods: One-hundred forty-six asthma patients and 150 control subjects were studied. DNA was extracted from peripheral blood samples.

Juvenile idiopathic arthritis subtype- and sex-specific associations with genetic variants in the PSMA6/PSMC6/PSMA3 gene cluster.

Background: The ubiquitin proteasome system plays an exceptional biological role in the antigen processing and immune response and it could potentially be involved in pathogenesis of many immunity-related diseases, including juvenile idiopathic arthritis (JIA).

Methods: The PSMB5 (rs11543947), PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827), and PSMA3 (rs2348071) proteasomal genes were genotyped on JIA subtype- and sex-specific association; plasma proteasome levels was measured in patients having risk and protective four-locus genotypes and eventual functional significance of allele substitutions was evaluated in silico.

Results: Loci rs11543947 and rs1048990 were identified as disease neutral and other loci as disease susceptible (p < 0.

Proteasomes and proteasomal gene polymorphism in association with inflammation and various diseases.

A proteasome, a multicatalytic protein complex, is a central particle of the ubiquitin-proteasome proteolytic pathway in all eukaryotic cells. Through the degradation of most intracellular proteins, proteasomes play a significant role in cell processes, such as cell cycle and division, posttranslational protein quality control, cell signaling, and apoptosis. Therefore, the ubiquitin-proteasome system is necessary to ensure the normal functioning of cells and an organism.

Comparison of the effects of glibenclamide on metabolic parameters, GLUT1 expression, and liver injury in rats with severe and mild streptozotocin-induced diabetes mellitus.

Background And Objective: Glucose transport via GLUT1 protein could be one of additional mechanisms of the antidiabetic action of sulfonylureas. Here, the GLUT1 gene and the protein expression was studied in rats in the course of severe and mild streptozotocin-induced diabetes mellitus and under glibenclamide treatment.

Material And Methods: Severe and mild diabetes mellitus was induced using different streptozotocin doses and standard or high fat chow.

Functional significance of microsatellite markers.

The review summarizes literature data on the positive results of association studies between the length of microsatellite repeats and predisposition to pathologies. Actually, the data can be classified according to the localization of the microsatellite: in the gene promoter, in the part of exon 1 coding the signal sequence, in gene introns, in the coding areas of genes, and in 3'-untranslated regions. The functional significance of microsatellite length changes can be evaluated in many cases.

The burden of allergic asthma in children: a landscape comparison based on data from Lithuanian, Latvian, and Taiwanese populations.

Asthma is one of the most common chronic respiratory diseases with an increasing prevalence and financial burden worldwide. This disease affects individuals in all countries and all ethnic groups; however, prevalence rates of asthma have been reported to vary significantly between different regions. To understand the origin of asthma and to manage it effectively, it is necessary to analyze the genetic and environmental factors that cause these geographic differences.

Analysis of the single-nucleotide polymorphism in the 5'UTR and part of intron I of the sheep MSTN gene.

The myostatin (MSTN) gene region encompassing the 5'UTR and part of intron I was sequenced in animals of two herds of Latvian Darkhead sheep to extend data on the ovine MSTN gene polymorphism and to provide information useful for local breed conservation. Two and four polymorphic loci were revealed in the 5'UTR and intron I. Four and five local haplotypes were constructed, respectively.

Correction of glycaemia and GLUT1 level by mildronate in rat streptozotocin diabetes mellitus model.

Anti-ischaemic drug mildronate suppresses fatty acid metabolism and increases glucose utilization in myocardium. It was proposed that it could produce a favourable effect on metabolic parameters and glucose transport in diabetic animals. Rats with streptozotocin diabetes mellitus were treated with mildronate (100 mg/kg daily, per os, 6 weeks).

Influence of metformin on GLUT1 gene and protein expression in rat streptozotocin diabetes mellitus model.

Context: Metformin improves hyperglycaemia via mechanisms which include activation of AMP-activated protein kinase (AMPK). Recent findings indicate that some metabolic actions of metformin occur also by AMPK-independent mechanisms.

Objective: To study the action of metformin on expression of GLUT1 glucose transporter in rat streptozotocin model of diabetes mellitus.

Identification of a novel candidate locus for juvenile idiopathic arthritis at 14q13.2 in the Latvian population by association analysis with microsatellite markers.

To identify novel juvenile idiopathic arthritis (JIA) susceptibility loci, a 270 kb genomic region encompassing FAM177A1, KIAA0391, and PSMA6 genes was genotyped in 97 oligoarthritis (JIoA) and 50 polyarthritis (JIpA) patients and 230 individuals without autoimmune disorders by five microsatellites (MS) previously described as HSMS markers of the 14q13.2 region. Direct sequencing revealed two variable components of the (CAA)(n)(A)(m) motif in HSMS602 marker (FAM177A1 gene).

Development-dependent changes in the tight DNA-protein complexes of barley on chromosome and gene level.

Background: The tightly bound to DNA proteins (TBPs) is a protein group that remains attached to DNA with covalent or non-covalent bonds after its deproteinisation. The functional role of this group is as yet not completely understood. The main goal of this study was to evaluate tissue specific changes in the TBP distribution in barley genes and chromosomes in different phases of shoot and seed development.

Transcription- and apoptosis-dependent long-range distribution of tight DNA-protein complexes in the chicken alpha-globin gene.

The proteins tightly bound to DNA (TBP) are a group of proteins that remain attached to DNA with covalent or noncovalent bonds after its deproteinization, and have been hypothesized to be involved in regulation of gene expression. To investigate this question further, oligonucleotide DNA arrays were used to determine the distribution of tightly bound proteins along a 100-kb DNA fragment surrounding the chicken alpha-globin gene domain in DNA from chicken erythrocytes, liver, and AEV-transformed HD3 (erythroblast) cells in different physiological conditions. DNA was fractionated into TBP-free (F) and TBP-enriched (R) fractions by separation on nitrocellulose, and these fractions were used as probes for hybridization with the microarray.

Putative role of nitric oxide synthase isoforms in the changes of nitric oxide concentration in rat brain cortex and cerebellum following sevoflurane and isoflurane anaesthesia.

We have previously observed an increase in nitric oxide (NO) content in rat brain cortex following halothane, sevoflurane or isoflurane anaesthesia. This study was undertaken in order to determine whether isoform-specific nitric oxide synthase (NOS) inhibitors and inducers could modify these increases in NO contents. Rats were subjected to isoflurane and sevoflurane anaesthesia with concomitant administration of neuronal nitric oxide synthase (nNOS) inhibitor 7-Nitro-indazole (7-NI), inducible nitric oxide synthase (iNOS) inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) or lipopolysaccharide.

Distribution of tight DNA-protein complexes along the barley chromosome 1H, as revealed by microsatellite marker analysis.

The distribution of DNA complexes with proteins resistant to routine deproteinisation procedures (tightly bound proteins, TBP) was studied on the barley chromosome 1H by means of microsatellite analysis. The polypeptide spectrum of the barley shoot TBP was similar to that formerly described for other organisms. In order to reveal developmental changes in the distribution of the TBP, DNA was extracted from dry grains, coleoptiles, root tips, and young and old leaves.