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Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM). Among the molecular mechanisms leading to the development of DR, the endoplasmic reticulum (ER) stress that is identified in DM in retinal neurons and in pericytes of retinal capillaries plays an important role. Abnormalities in the folding and maturation of proteins in ER trigger the ER specific response, referred as the unfolded protein response (UPR), which induces protein refolding or degradation. Currently, there are three main UPR-pathways that include inositol-requiring enzyme-1 (IRE1), transcription factor-6 (ATF6) and sensory kinase PERK as the sensor components, all of which are involved in the pathological changes in the retina at DR, inducing the inflammation, apoptosis and vascular impairment therein. In the review, the functional changes in IRE1-, ATF6and PERK-dependent UPR-pathways in diabetic retina, as well as factors that contribute to the development of ER stress in retinal cells including pro-inflammatory factors, vascular endothelial growth factor and intercellular adhesion molecules are considered. The approaches to ER stress correction in diabetic retina, which include the use of low-molecular chaperones, such as fenofibric acid, increased activity of chaperone-like p58IPK protein, and the restoration of activity of retinal hormonal signaling systems, whose functions are violated in DR, are discussed.

The interferon (IF) and cell-apoptosis (CA) systems are interrelated and regulate the protective reactions in body by means of a complex of biologically active proteins. The transcription levels of mRNA were determined by the RT-PCR semi-quantitative method in order to compare the constitutive expression levels of IF (alpha, beta, gamma) genes, IF-dependent enzymes of 2'5'-oligoadenylatesynthetyase (OAS), RNAase L, dsRNA-protein kinase (dsPK) and CA effectors (Fas-Ag, bcl-2 and gamma-actin) in human blood microsamples. cDNA dilutions, different numbers of amplification cycles (PCR with specific pairs of primers) as well as PCR-products' dilutions for dot-hybridization with specific probes were made use of to detect and evaluate levels of 9 mRNAs. The constitutive levels of gene expression of the IF and CA systems were found to differ essentially from others (1000-fold). The studied mRNA types were shared between 5 groups according to their transcription levels: very high--alpha-IF, high--RNAase L, medium--gamma-actin and bcl-2, low--beta-IF and very low (detectable after induction only)--gamma-IF, OAS, dsPK and Fas-Ag. The used detection method has a sufficiently high sensitivity and can be recommended for studies of IF inductors with unknown action mechanisms.

The active replication of Karelian fever virus (KFV) in human blood vessels and the protective activity of the Russian agent reaferon were first shown. KFL was highly susceptible to interferon (IFN)-alpha. In control (uninfected) cells, reaferon caused low gene expressions of the IFN-dependent enzymes dsRNA-dependent protein kinase and 2'5'-oligoadenylate synthetase, by exerting a little effect on the activity of its family genes. KFV suppressed the reaferon-induced gene expression of IFN-dependent enzymes, but IFN-alpha gene transcription was increased in the reaferon-treated infected cells.

In this review recent data describing stress granules are summarized. Stress granules are specific RNA-containing structures in the cytoplasm of living cells which arise under stress conditions (e. g. heat shock, UV irradiation, energy depletion and oxidative stress). It became evident that stress granules accumulate non-canonical 48S initiation complexes and contain mRNA with associated proteins, small ribosomal subunits and some initiation factors. Stress granules are depleted with ternary complex and large ribosomal subunit. It's proposed that eIF2alpha phosphorylation and ternary complex decrease can be a trigger for stress granule formation. Shuttling nuclear and cytoplasmic RNA-binding protein TIA-1 plays a crucial role in this process. It's proposed that TIA-1 forms prion-like aggregates, and these aggregates are scaffolds for other components of stress granules. Cytoskeletal structures facilitate the accumulation of stress granule components in local cytoplasmic sites. Investigation of process of stress granule formation is important for understanding of cell reaction to stress and translation regulation mechanisms.

Expression of 2,5-OAS and ds-protein kinase (ds-PK) in human fibroblast culture following treatment with alpha-IF in a dose of 1000 U or challenge with Karelian fever virus (KFV) (5 PFU/cell, 4 h.p.i.) was compared. A highly sensitive and rapid method, coupled RT-PCR, was used to detect mRNA transcription levels. Alpha-IF had an expressed stimulating effect on 2,5-OAS mRNA level, whereas the virus markedly inhibited the synthesis of ds-PK mRNA.