Main mechanisms of the initiation and development of diabetic complications: the role of nitrative stress

In the review described the main mechanisms of the oxidative stress initiation in the mitochondria electron-transport chain under the hyperglycaemia condition. It is described the main metabolic and signal-transduction mechanisms, activation of which takes place under the chronic diabetic complications, and which leads to the increase of oxidative stress. It is analised in detail the role of nitric oxide in the biological systems and its properties under the condition of oxidative stress, especially under the diabetes mellitus. The results of the main biological targets for the peroxinitrite and the molecular markers of the diabetic complications were summarized

Nephroprotective effect of grape wine in the rat with experimental diabetes mellitus

It was established that polyphenols of red and white grape wines completely or partially normalize kidney weight to body weight ratio, the level of nitrotyrosine modified proteins and activity of poly-ADP-ribose polymerase-1 in the kidney of rats with diabetes mellitus, compared with diabetic animals without wine consumptions

The antioxidant effect of natural polyphenolic complexes of grape wine in the rat retina under streptozotocin-induced diabetes mellitus

The protective effects of natural polyphenolic complexes of the grape wine on antioxidant system in retinae of rats under streptozotocin-induced diabetes mellitus are established. It was shown that proposed level of polyphenol speciment of the grape wine that was consumed did not change blood glucose concentrations in control and diabetic groups of animals. During the experiment the body weight of control group and diabetic groups of rats with consumption of studied speciment was significantly increased. The polyphenols completely or partially normalized the work of enzymatic antioxidant system (superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase). It was shown that level of products of lipid peroxidation in the groups of rats with and without consumption of polyphenol speciment differed significantly. The presented results allow to suggest an important role of speciment of grape wine in preventing and treatment of diabetes retinopathy

Intra- and intermolecular interactions mediated by adaptor protein Ruk/CIN85/SETA

Ruk/CIN85l SETA is a member of a separate and evolutionary conserved family of adapter I scaffold proteins implicated in apoptic and receptor tyrosine kinases signalling, rearrangement of actin cytoskeleton and cell adhesion, podocyte and T cell functions. Self-regulation through intra- and intercellular interactions can be supposed for RuklCIN85l SETA as this protein contains SH3 domains and proline-rich sequence, localized within one polypeptide chain, as well as C-terminal coiled-coil region. The ability of Ruk proline-rich motifs to interact with its own SH3 domains in an intramolecular fashion and coiled-coil region to mediate oligomerization between different isoforms was assessed in GST pull down experiments. It was shown that both Ruk SH3A and to a less extent SH3B domains can interact with its own proline-rich sequences in a cooperative manner, while coiled-coil region provide for isoforms oligomerization. SH3C domain appear exerts conformational constraints, imposed on coiled-coil region, restricting the level of oligomerization. We also demonstrated that the ability of exogenous ligands to interact with Ruk polyprotine motifs is changing during the course of TNFa-induced apoptosis of human myelomonocytic W37 cells