Epstein barr virus EBNA1 and LMP1 recombinant proteins effect on the endoplasmic reticulum (ER) stress markers, apoptosis and proliferation in the INS1-E (832/13) beta cell culture

The prevalence and incidence of diabetes is a health problem that increases almost every day today's world. Although humoral and histologic findings of diabetes complications are diverse; the high numbers of complications cause the diagnosis and treatment of diabetes to be extremely important. Today, it is believed that a large number of diseases, including diabetes, are related to the Endoplasmic Reticulum (ER) stress-induced apoptosis. Indeed, it is emphasized that studies in pancreatic beta cells and folding capacity of the ER organelle protein intake resulting from the imbalance between the apoptosis induced by ER stress caused by diabetes. Epstein-Barr Virus (EBV); Lenfocriptovirüs is a virus, such viruses in general the latent infection in B lymphocytes during periods of cell proliferation and are known to contribute to the transformation process. Proliferative activity of EBV proteins occurs via two mediators (Epstein Barr Nuclear Antigen1-EBNA1 and latent membrane Protein1-LMP1). Type 2 diabetic patients treated for a long time during the anti-diabetic pancreatic cell loss and resulting decrease in pancreatic mass lead to the use of exogenous insulin. In this study, it is aimed to investigate that recombinant viral EBV protein of pancreatic cell loss those applying to reverse. In addition to that related proteins as well as DNA damage and stress effects on insulin synthesis and release and their contributions were also investigated. For that purpose, commercially obtained recombinant proteins LMP1 Lethal Dose 50 EBNA1 and after operation 0.1 ppm and 0.5 ppm doses of either protein, were decided to be studied. Upon application of these proteins indicated dose proliferation is affected by this order to determine to what extent they are known to be responsible for the proliferation of mRNA expression levels of genes was investigated. Comet assay for DNA damage and on the other hand to ER stress, levels of mRNA expression of the gene of interest were tested. As a result of RT-PCR applications, mRNA expression levels of genes of AFT4, ATF6, PERK, GRP78 and CHOP, which are ER stress markers, orderly increased 10-fold, 19-fold, 15,03-fold, 6,63-fold, and 8,05-fold according to DMSO control group in thapsigargin group. It is observed this increase on the expression of the genes which are ER stress marker is repressed by interest proteins. As a result; the conclusion was that EBV recombinant proteins LMP1 and EBNA1 proliferation genes which are responsible for expression levels increased but also ER stress marker gene expression level by suppressing the ER stress-induced beta cell loss in reversing would be advantageous and therefore higher levels work and if supported antidiabetic treatments virotherapy as agents the ability to use the potential opening of the way.