The effect of endoplasmic reticulum stress response markers and apoptotic marker C-EBP homologous protein levels in patients of COVİD-19

The increased requirement for protein synthesis in cells disrupts the correct folding capacity of structural or functional proteins. As a survival strategy, cells try to rearrange their protein folding capacity in line with the increased protein folding need. In the period until this regulation is achieved, misfolded proteins accumulate in the stressed cell; It triggers a series of transcriptional and translational processes associated with the endoplasmic reticulum (ER) known as the "misfolded protein response (UPR) pathway". In chronic stress, the UPR pathway is at a key point in both the cause and treatment of many abnormalities, as it can pave the way for the cell to eliminate itself through apoptosis by activating another terminating plan instead of the regulator. In our study, the levels of ER stress response markers GRP78, PERK, eIF2alpha, ATF4, GADD34, CHOP and miRNA-199 were studied in the SARS-CoV-2 model. For this purpose, 74 patients who were hospitalized with a diagnosis of COVID-19 using ARDS and PCR criteria and 26 healthy control volunteers were included. According to termination patients were grouped as n = 49 Survival group and n = 25 as Ex group. In our study, GRP78 and PERK remained high and activated UPR, respectively, in case of infection, regardless of the amount of viral load, and the increase in GADD34 protein with eustress in the Survival group resulted in strong inhibition of eIF2α, which resulted in suspended protein translation in the cell. It was found to cause the removal of inhibition, re-synthesis of cellular proteins and reduction of the apoptotic marker CHOP. In the Ex group, it was found that the decrease in GADD34 value from the first measurement to the last measurement caused eIF2α not to be suppressed, cellular protein translation stopped, and ATF4, one of the proteins associated with survival, increased significantly, and this increase caused the apoptotic protein CHOP to increase gradually, dragging the cell into apoptosis.