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- Title
ДИЗРЕГУЛЯЦІЯ АУТОФАГІЇ У ЛЕЙКОЦИТАХ ПЕРИФЕРИЧНОЇ КРОВІ ЯК ФАКТОР РОЗВИТКУ ІНФЛАМЕЙДЖИНГУ В ІМУНОСКОМПРОМЕТОВАНИХ ОСІБ НА ПРИКЛАДІ ВІЙСЬКОВОСЛУЖБОВЦІВ СИЛ ОБОРОНИ УКРАЇНИ ТА УЧАСНИКІВ ЛІКВІДАЦІЇ НАСЛІДКІВ АВАРІЇ НА ЧАЕС
- Authors
Зварич, Л. М.; Базика, Д. А.
- Abstract
Objective. To assess the functional state and age&related characteristics of autophagy in peripheral blood leuko& cytes as a risk factor for the development of inflammaging using the example of the servicemen of the Defense Forces of Ukraine and clean&up workers of the Chornobyl accident. Materials and methods. A total of 103 male patients aged 28-77 (56,48 ± 9,05) years were examined. They includ& ed: the main group - 23 servicemen of the Defense Forces of Ukraine aged 44-59 (50,21 ± 5,13) years; the compari& son group - 57 clean&up workers of the Chornobyl accident aged 56-63 (60,31 ± 1,78) years; and the control group - 23 civilians aged 28-77 (53,26 ± 15,98) years. The individuals in the main and control groups were divided accord& ing to age into subgroups under 50 years and over 50 years. Clean&up workers were divided into 3 subgroups depend& ing on the radiation dose: І - D 500 mSv. Analysis of autophagy parameters in peripheral blood leukocytes (PB) was performed using flow cytometry and polymerase chain reaction. Results. In patients of the main group, the autophagy activity factor (AAF) of granulocytes and the expression of the SQSTM1 gene in PB leukocytes decreased. A decrease in chloroquine&induced accumulation of LC3B protein in leuko cytes, AAF in PB monocytes and the expression of the MTOR, RB1CC1 and MAP1LC3B genes was revealed in servicemen of the Defense Forces of Ukraine under 50 years of age. The spontaneous levels of LC3B protein and AAF in monocytes and the expression level of PIK3C3, ULK1 and MAP1LC3B genes in PB leukocytes were increased in servicemen of the Defense Forces of Ukraine over 50 years of age. The cleanup workers of different dose groups showed a decrease in the AAF in lymphocytes and granulocytes, the LC3B level in monocytes after incubation with chloroquine, the expres& sion of the MTOR, RB1CC1, SQSTM1, ULK1, MAP1LC3B, BECN1 and PIK3C3 genes in PB leukocytes, and the AAF of mono cytes was higher. Similar changes were revealed in the indices of chloroquine&induced LC3B accumulation in lympho& cytes and monocytes of the clean&up workers and servicemen of both age groups, as well as the spontaneous LC3B pro& tein level in PB monocytes of the clean&up workers irradiated at doses above 100 mSv and civilians over 50 years old. Conclusions. Unidirectional dysregulation of autophagy was established in the servicemen of the Defense Forces of Ukraine and the clean&up workers of the Chornobyl accident. The existing changes in autophagy parameters can lead to disruption of the functioning of the autophagic apparatus of leukocytes at the level of mRNA and protein, as well as signaling pathways, and be associated with age related changes at both the cellular and organismal levels. The emergence of new and persistent earlier stress factors as a result of the war creates an additional load on the mech& anisms of maintaining homeostasis, which is observed in individuals exposed to ionizing radiation more than 30 years later. The found intergroup differences and similarities can activate the same or similar mechanisms of patho logical processes, which will ultimately increase the risks of developing age&associated chronic somatic pathology in younger age groups.
- Subjects
HOMEOSTASIS; GENE expression; AGE groups; IONIZING radiation; POLYMERASE chain reaction
- Publication
Problems of Radiation Medicine & Radiobiology, 2024, Issue 29, p327
- ISSN
2304-8336
- Publication type
Academic Journal
- DOI
10.33145/2304-8336-2024-29-327-358