Early and late responses to oxidative stress in human dermal fibroblasts of healthy donors and rheumatoid arthritis patients. Relationship between the cell death rate and the genomic dosage of active ribosomal genes

Active ribosomal genes, translational homeostasis and oxidative stress in the pathogenesis of schizophrenia and autism

“…Earlier, we conducted a number of experiments aimed at studying the impact of oxidative stress on cultured cells derived from both healthy donors and RA patients. This study showed a close relation between the resistance of cells to the impact of oxidative stress and the copy number of transcriptionally active rRNA genes (ribosomal genes) in the cell genome (Veiko et al, 2005). The number of active ribosomal gene copies in a test sample of RA patients (n = 49) varied from 14.4 to 20.7 AU, with a mean of 17.6 0.2 (SE) AU.…”

“…In our case, the model takes into account that the antioxidant enzyme molecules y do not reproduce themselves, but are synthesized in proportion with oxidative stress x. Indeed, under the conditions of oxidative stress induced in vitro by potassium chromate, as we reported earlier (Veiko et al, 2005), the amount of newly synthesized rRNA and, hence, the number of ribosomes engaged in the protective protein translation, within certain limits, increased linearly as the concentration of potassium chromate increased. In the same earlier work, we showed that the rate of the survival of cells after an oxidative stress impact ('late' response) depended directly on the copy number of active rRNA genes in the cell line genome.…”

“…In our earlier in-vitro experiments on human fibroblasts, we registered the 'early' response to oxidative stress, which included the activation of transcription of ribosomal genes (genes for rRNA) and an increase in the amount of total RNA and rRNA in the cells during the first 1.5-2 h of the experiment. It provides the cell cytoplasm with new ribosomes necessary for the synthesis of the set of antistress protective proteins (Veiko et al, 2005). Moreover, the intensity of the early response and, hence, the cell's capability to cope with stress was found to be proportional to the copy number of active ribosomal genes in the cell's genome.…”

Oxidative stress, rRNA genes, and antioxidant enzymes in pathogenesis of schizophrenia and autism: Modeling and clinical recommendations

“…Consequently, the amount of AcRG, which provides for the intensity of protein synthesis in the cell, in individual human genomes varies from 120 to 190 copies with an average value of approximately 150 copies. This is an important feature of the genome, which has a variety of phenotypic manifestations (Veiko et al, 2005;Neudakhin et al, 2008;Lyapunova et al, 2000;Morukov et al, 2008). In particular, the fewer transcriptionally active RG copies there are, the less pronounced is the cell's ability for the rapid syn thesis of proteins needed to overcome the effects of stress.…”

“…This response is expressed in the activation of transcription of riboso mal genes (rRNA genes) and an increase in the amount of total RNA and rRNA in the cells during the first 1.5-2 h of the experiment. It provides the emer gence in the cytoplasm of new ribosomes required for the synthesis of a complex of antistress protection pro teins (Veiko et al, 2005). It has been shown that the magnitude of the early response and hence the cell's ability to overcome the stress are proportional to the number of copies of active ribosomal genes in the genome of the cell.…”