[Proteasomal degradation of ribonucleic acids of different NO-synthase isoforms].

Using a developed method of determination of the RNase activity of the proteasome in vitro with the application of reverse transcription followed by subsequent polymerase chain reaction it was shown that 26S proteasome from the proteasomal fraction II effectively cleaves RNA, encoding actin, myosin and all isoforms of NO synthase. The intensity of RNA degradation by proteasome and specific RNases is similar. It was also shown that clasto-lactacystin beta-lactone, a specific proteasome inhibitor significantly depresses RNase activity of the proteasome.

[Allelic polymorphism of genes encoding catalytic immunoproteasome subunits and its functional meaning].

Proteasomal activity in isolated monocytes from subjects with different variants of large multifunctional proteases genes -LMP2 (Arg60-->His allelic polymorphism) and LMP7 (Lys145-->Gln allelic polymorphism) was determined. Trypsin-like activity of proteasome was 1.6-times (P = 0.

[Allelic polymorphism of endothelial NO-synthase gene and its functional activity].

Investigation of phenotypic realization of the eNOS gene allelic polymorphism has shown that eNOS RNA content and eNOS activity in platelets depends on genotype. Using the reverse transcription and polymerase chain reaction it was shown that eNOS mRNA content is the lowest at -786C/C promoter's genotype. In exon 7 homozygotes (894T/T) the RNA level is lower than in normal homozygotes (894G/G), but it is higher than in heterozygotes (894G/T).

[Allelic polymorphism of endothelial NO-synthase (T(-786)-->C) promoter gene as risk factor of acute coronary syndrome].

Frequency of promoter endothelial NO-synthase gene allelic polymorphism by using polymerase chain reaction and restriction fragment length polymorphism (RFLP-PCR) was determined in 221 patients with acute coronary syndrome (ACS) and in 83 almost healthy subjects. Data obtained indicate that different promoter allelic variant frequency differs significantly in patients with ACS and in control group. Correlation of normal homozygotes (T/T), heterozygotes (T/C) and pathologic homozygotes (C/C) was 48%, 36% and 16% respectively in patients, and in control it was 48%, 46%, 6% (P<0.

[Pathophysiologic aspects of endothelial NO-synthase genetic polymorphism].

Information about fourteen allelic variants of promoter, exons and introns of a gene of endothelial NO-synhase (eNOS) dealing with their role in a susceptibility to cardio-vascular diseases has been reviewed. Data of the populational genetic studies, performed in different regions of the world, were analysed to show the interrelation between an availability of on allele in the genome and a risk of ischemic heart disease. The main attention was focussed on the clarification of a relation between some allelic variants of the gene and functional (biochemical) properties of the protein, encoded by this gene, as well as on two principal mechanisms of realization of the pathological allelic variants in eNOS gene: 1) forming the protein in an insufficient quantity or with an altered activity (an interrupted transcription, and stability of informational RNA, formation of a cathalitically deficient protein); 2) an increased protein degradation (due to an acidic hydrolysis or an enhanced proteasomal proteolysis).