Title: P3‐186: Expression of 8‐oxoguanine DNA glycosylase 1 (OGG1) and the level of p53 and TNF‐alpha proteins in peripheral lymphocytes in patients with Alzheimer's disease
Abstract: Reactive oxygen species are highly reactive and may oxidize especially nucleic acids (DNA). 8-Oxo-2'-deoxyguanosine (8-oxo2dG) is one of the crucial lesions produced in DNA by oxygen radical-forming agents. OGG1 is a main DNA repair enzyme that excises 8-oxo2dG from DNA. It was postulated that decreased expression of OGG1 may lead to higher background mutation frequency and could increase the DNA damages risk. 8-Oxo2dG is known to induce GC-TA transversion type point mutations, and this type of mutation is commonly observed in the tumor suppressor p53 gene. Moreover, in mice OGG1 coupled with lower level of TNF-alpha. Damage of genomic DNA may lead to the cell death by apoptosis in results it causes degenerative disorders. P53 and TNF-alpha may induce apoptotic process in the cells. The studies were conducted on 41 patients with AD, including 25 women and 16 men aging 34-84 years. The control groups included 51 individuals, 20 women and 31 men aging 22-83 years. The level of 8-oxo2dG was determined using HPLC/EC/UV technique and the level of OGG1 and p53, TNF-alpha proteins was determined with Western Blot method. We were observed increase of the level of 8-oxo2dG after 60 years of age (insignificant) and in AD patients (p < 0.05) as compared to the controls. Simultaneously, the levels of OGG1 and TNF-alpha proteins were decreased in individuals after 60 years of age (OGG1, p < 0.01; TNF-alpha, p < 0.05) and in AD patients (OGG1, p < 0.001; TNF-alpha, p < 0.05) as compared to the controls when the level of p53 protein was increased in individuals after 60 years as well as in AD patients (Mann-Whitney test, p < 0.05) as compared to the controls. However, in patient with mild dementia (in MMSE scale) were observed the lowest level of 8-oxo2-dG and OGG1 and the highest levels of p53 and TNF-alpha proteins, when in the patients with moderate dementia (in MMSE scale) were observed the highest level of OGG1 (p < 0.05, as compared to the patient with mild dementia) and the lowest level of TNF-alpha. It is possible that OGG1 and p53 and TNF-alpha proteins are involved in pathogenesis of AD by repair of oxidative DNA damage and apoptosis.