Аннотация
Различные механизмы клеточной гибели играют определённую роль в патогенезе заболеваний полости рта, ассоциированных со старением, такими как хронический генерализованный пародонтит (ХГП) и красный плоский лишай (КПЛ). Маркёры апоптоза, определяемые в ротовой жидкости (РЖ), могут быть ценным инструментом в диагностике этих заболеваний, представляют интерес в качестве биомаркёров старения. Цель — оценить взаимосвязь механизмов апоптоза с возраст-ассоциированными стоматологическими заболеваниями — ХГП и КПЛ. Обследованы 78 человек. Контрольная группа представлена здоровыми добровольцами молодого возраста (n=22), группа сравнения — относительно здоровыми лицами пожилого возраста (n=10). Выделена группу пациентов пожилого возраста с ХГП средней степени тяжести (n=10) и группу пожилого возраста с КПЛ (n=10). Пациенты зрелого возраста сформировали группу с ХГП лёгкой (n=16) и с ХГП средней степени тяжести (n=10). В РЖ определяли белок bcl-2, цитохром с (cyt-c), фермент глицеральдегид-3-фосфатдегидрогеназу (GAPDH) методом мультипараметрического флуорисцентного анализа с магнитными микросферами (xMAP, Luminex 200, USA), тест-система ProcartaPlex Human Apoptosis Panel 6-Plex (Invitrogen, USA). Установлено, что пациенты пожилого возраста с КПЛ отличались наиболее высоким содержанием cyt-c в РЖ. Пациенты пожилого возраста с ХГП имели концентрацию cyt-c выше, чем группы пациентов зрелого возраста с ХГП лёгкой и средней степени тяжести. Пациенты зрелого возраста с ХГП отличались от контрольной группы боле низким уровнем cyt-c и GAPDH в РЖ. Уровень саливарного cyt-c представляет интерес в диагностике КПЛ у пациентов пожилого возраста. Cyt-c и GAPDH РЖ могут иметь ценность в выявлении пациентов зрелого возраста с ХГП. Предполагаем, что cyt-c может являться биомаркёром ускоренного патологического старения тканей полости рта.
Annotation
Cell death plays a significant role in the pathogenesis of oral age-related disease, such as chronic periodontitis (CP) and oral lichen planus (OLP). Apoptosis biomarkers in saliva can be a useful method of these diseases diagnostic, and are also interesting as biomarkers of aging. The aim of the study was to evaluate the relationship of apoptosis mechanisms with oral age-related diseases — CP and OLP. The study included 78 people. The control group included 22 healthy young volunteers. The comparison group included 10 healthy elderly people. A group of elderly patients with moderate CP (n=10) and an elderly patients group with OLP (n=10) were formed. Mature patients formed a group with mild CP (n=16) and moderate CP (n=10). Bcl-2 protein, cytochrome c (cyt-c) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined in saliva samples by multiparametric fluorescence analysis with magnetic microspheres (xMAP, Luminex 200, USA), the ProcartaPlex Human Apoptosis Panel 6-Plex (Invitrogen, USA) test system. It was found that salivary cyt-c content was highest in OLP elderly patients. Salivary concentration of cyt-c in elderly patients with CP was higher than in the mature patients with mild and moderate CP. Salivary levels of cyt-c and GAPDH in mature patients with CP were lower than in the control group. Thus, the concentration of salivary cyt-c is interesting in OLP diagnostic of elderly patients. Salivary cyt-c and GAPDH may be useful in mature patients with CP identifying. We believe that cyt-c in saliva may be a potential biomarker of accelerated pathological aging of oral tissues.
Список литературы
1. Raphael C. Oral Health and Aging. Am. J. Public Health. 2017; 107(S1): S44-S45.
2. Ebersole J.L, Dawson D.A. 3rd, Emecen Huja P., Pandruvada S., Basu A., Nguyen L. et al. Age and Periodontal Health — Immunological View. Curr. Oral. Health Rep. 2018; 5(4): 229-41.
3. Mutafchieva M.Z., Draganova-Filipova M.N., Zagorchev P.I., Tomov G.T. Oral Lichen Planus — Known and Unknown: a Review. Folia Med. (Plovdiv). 2018; 60(4): 528-35.
4. Ide M., Karimova M., Setterfield J. Oral Health, Antimicrobials and Care for Patients With Chronic Oral Diseases — A Review of Knowledge and Treatment Strategies. Front. Oral Health. 2022; 3: 866695.
5. Chen S., Zhou D., Liu O., Chen H., Wang Y., Zhou Y. Cellular Senescence and Periodontitis: Mechanisms and Therapeutics. Biology (Basel). 2022; 11(10): 1419.
6. Childs B.G., Baker D.J., Kirkland J.L., Campisi J., van Deursen J.M. Senescence and apoptosis: dueling or complementary cell fates? EMBO Rep. 2014; 15(11): 1139-53.
7. Ward T.H., Cummings J., Dean E., Greystoke A., Hou J.M., Backen A. et al. Biomarkers of apoptosis. Br. J. Cancer. 2008. 99(6): 841-6.
8. Czabotar P.E., Lessene G., Strasser A., Adams J.M. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat. Rev. Mol. Cell Biol. 2014; 15(1): 49-63.
9. Ryu S.J., Oh Y.S., Park S.C. Failure of stress-induced downregulation of Bcl-2 contributes to apoptosis resistance in senescent human diploid fibroblasts. Cell Death. Differ. 2007; 14(5): 1020-8.
10. Childs B.G., Durik M., Baker D.J., van Deursen J.M. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat. Med. 2015; 21(12): 1424-35.
11. Santucci R., Sinibaldi F., Cozza P., Polticelli F., Fiorucci L. Cytochrome c: An extreme multifunctional protein with a key role in cell fate. International journal of biological macromolecules. 2019; 136, 1237-46.
12. Bock F.J., Tait S.W.G. Mitochondria as multifaceted regulators of cell death. Nature reviews. Molecular cell biology. 2020; 21(2): 85-100.
13. Tristan C., Shahani N., Sedlak T.W., Sawa A. The diverse functions of GAPDH: views from different subcellular compartments. Cell Signal. 2011; 23(2): 317-23.
14. Nicholls C., Li H., Liu J.-P. GAPDH: A common enzyme with uncommon functions. Clinical and Experimental Pharmacology and Physiology. 2012; 39(8): 674-9.
15. Moritz C.P. Tubulin or Not Tubulin: Heading Toward Total Protein Staining as Loading Control in Western Blots. Proteomics. 2017; 17(20): 1600189.
16. Bazarnyi V.V., Mandra Yu.V., Kopenkin M.A., Abdulkerimov T.K., Maximova A.Yu., Polushina L.G. Impairment of the balance of angiogenic and neurogenic polypeptides of the oral fluid in fractures of the maxilla. Ural`skiy meditsinskiy zhurnal. 2023; 22(1):57-62. (in Russian)
17. Eke P.I., Dye B.A., Wei L., Thornton-Evans G.O., Genco R.J. et al. Prevalence of periodontitis in adults in the United States: 2009 and 2010. J. Dent. Res. 2012; 91(10): 914-20.
18. Greystoke A., Hughes A., Ranson M., Dive C., Cummings J., Ward T. Serum biomarkers of apoptosis. European Journal of Cancer Supplements. 2007; 5(5): 115-27.
19. Jiang S., Moriarty-Craige S.E., Li C., Lynn M.J., Cai J., Jones DP et al. Associations of plasma-soluble fas ligand with aging and age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2008; 49(4): 1345-9.
20. Li J., Verhaar A.P., Pan Q., de Knegt R.J., Peppelenbosch M.P. Serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) predict severity of liver disease in chronic hepatitis B. Clin. Exp. Gastroenterol. 2017; 10: 203-9.
21. Pradeep A.R., Suke D.K., Prasad M.V., Singh S.P., Martande S.S., Nagpal K. et al. Expression of key executioner of apoptosis caspase-3 in periodontal health and disease. J. Investig. Clin. Dent. 2016; 7(2): 174-9.
22. Bazarnyi V.V., Kopenkin M.A., Polushina L.G., Maximova A.Yu., Sementsova E.A., Mandra Yu.V. Significance of salivary poly (ADP-ribose)-polymerase in the assessment of age-dependent pathological processes in the oral cavity. Biomeditsinskaya khimiya. 2023; 69(2): 125-32.
23. Basu A. The interplay between apoptosis and cellular senescence: Bcl-2 family proteins as targets for cancer therapy. Pharmacol. Ther. 2022, 230: 107943.
24. Figueredo C.M., Alves J.C., de Souza Breves Beiler T.F.C., Fischer R.G. Anti-apoptotic traits in gingival tissue from patients with severe generalized chronic periodontitis. J. Investig. Clin. Dent. 2019, 10(3): e12422.
25. Leyva-Huerta E.R., Ledesma-Montes C., Rojo-Botello R.E., Vega-Memije E. P53 and bcl-2 immunoexpression in patients with oral lichen planus and oral squamous cell carcinoma. Med. Oral Patol. Oral Cir. Bucal. 2012; 17(5): e745-50.
26. Pigatti F.M., Taveira L.A., Soares C.T. Immunohistochemical expression of Bcl-2 and Ki-67 in oral lichen planus and leukoplakia with different degrees of dysplasia. Int. J. Dermatol. 2015; 54(2): 150-5.
27. Pessoa J. Cytochrome c in cancer therapy and prognosis. Biosci. Rep. 2022; 42(12): BSR20222171.
28. Roopashree M.R., Gondhalekar R.V., Shashikanth M.C., George J., Thippeswamy S.H., Shukla A. Pathogenesis of oral lichen planus—a review. J. Oral Pathol. Med. 2010; 39(10): 729-34.
29. Ikegami K., Yamashita M., Suzuki M., Nakamura T., Hashimoto K., Kitagaki J. et al. Cellular senescence with SASP in periodontal ligament cells triggers inflammation in aging periodontal tissue. Aging (Albany NY). 2023; 15(5): 1279-305.
30. Kebschull M., Guarnieri P., Demmer R.T., Boulesteix A.L., Pavlidis P., Papapanou P. N. Molecular differences between chronic and aggressive periodontitis. Journal of dental research. 2013; 92(12): 1081-8.
31. Xu X., Zhang T., Xia X., Yin Y., Yang S., Ai D. et al.. Pyroptosis in periodontitis: From the intricate interaction with apoptosis, NETosis, and necroptosis to the therapeutic prospects. Front. Cell. Infect. Microbiol. 2022; 12: 953277.
32. Tristan C., Shahani N., Sedlak T.W., Sawa A. The diverse functions of GAPDH: views from different subcellular compartments. Cell. Signal. 2011; 23(2): 317-23.
33. Fortes M.A.S., Marzuca-Nassr G.N., Vitzel K.F., da Justa Pinheiro C.H., Newsholme P., Curi R. Housekeeping proteins: How useful are they in skeletal muscle diabetes studies and muscle hypertrophy models? Analytical Biochemistry. 2016; 504: 38-40.