β2 Мicroglobulin and the aging process.


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The problems of longevity increase and its quality improvement are actual for the modern gerontology. So far it is necessary to complete tasks of early diagnostic and target prophylactic of the age-associated pathology. There are presented the data concerning β-microglobulin (β2М), one of the frequent marker of aging. There are considered the data about the structure, properties, and functions of β2М, in which concentration is increased by aging. The experiments demonstrated the β2М concentration to increase in the hippocampus of old animals as in young heterochronic parabionts. The great correlation is observed between the β2М concentration and the deterioration of cognitive functions as well as the development of dementia. β2М plays a great role in the development of cardiovascular disease. The heart ischemic disease, the pathology of arteria carotis and peripheral vessels were more expressive in the patients with a great β2М concentration in plasma. It was the correlation between diabetes mellitus severity and high β2М level. β2М, as an oncogenic factor, stimulates the development and metastasis of the different cancers. The determination of plasma β2М concentration is of great significance for the predictive medicine and the prophylactic of the age-associated pathology.

Full Text

Restricted Access

About the authors

B. I Kuznik

Chita State Medical Academy; Innovation Clinic of the Academy of Health

N. I Chalisova

Pavlov Institute of Physiology; Saint Petersburg Institute of Bioregulation and Gerontology

References

  1. Кузник Б.И., Давыдов С.О., Поправка Е.С., Линькова Н.С., Козина Л.С., Хавинсон В.Х. Эпигенетические механизмы пептидной регуляции и нейропротекторный белок FKBP1B. Молекулярная биология. 2019; 53 (2): 339-48
  2. Хавинсон В.Х., Кузник Б.И., Рыжак ГА. Пептидные биорегуляторы - новый класс геропротекторов. Успехи геронтологии. 2013; 26 (1): 20-37
  3. Чалисова Н.И., Концевая Е.А., Войцеховская М.А., Рыжак ГА. Влияние коротких пептидов на развитие органотипической культуры ткани кожи молодых и старых крыс. Профилактическая и клиническая медицина. 2011; 2 (2): 110-3
  4. Annweiler Cedric, Bataille Regis, Ferriere Nicolas, Douillet Bruno Delphine, Fantino Beauchet Olivier. Plasma Beta-2 Microglobulin as a Marker of Frailty in Older Adults: A Pilot Study. The J. of Gerontology. 2011; 66A (10): 1077-79. https://doi. org/10.1093/gerona/glr104.
  5. Brew B.J., Dunbar N., Pemberton L., Kaldor J. Predictive markers of AIDS dementia complex: CD4 cell count and cerebrospinal fluid concentrations of beta 2-microglobulin and neopterin. The J. of infectious diseases. 1996; 174: 294-98.
  6. Carrette O. A panel of cerebrospinal fluid potential biomarkers for the diagnosis of Alzheimer's disease. Proteomics. 2003; 3: 1486-94.
  7. Villeda S.A., Luo J., Mosher K.I. The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature. 2011; 477: 90-4.
  8. Hilt Z.T, Ture S.K., Mohan A., Arne A., Morrell C.N. Platelet-derived p2m regulates age related monocyte/macrophage functions. Aging (Albany Ny). 2019; 11. https://doi. org/10.18632/aging.102520.
  9. Smith L.K., He Y, Park J.S., Bieri G., Snethlage C.E., Lin K., Gontier G., Wabl R., Plambeck K.E., Udeochu J., Wheatley E.G., Bouchard J., Eggel A., Narasimha R., Grant J.L., Luo J., Wyss-Coray T., Villeda S.A. P2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis. Nat Med. 2015; 21 (8): 932-7. https://doi.org/10.1038/nm.3898.
  10. Villeda S. A., Plambeck, K. E., Middeldorp, J. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature Medicine. 2014; 20 (6): 659-63.
  11. Das M.M., Godoy M., Chen S., Moser V.A., Avalos P, Roxas K.M., Dang I., Yanez A., Zhang W., Bresee C., Arditi M., Liu G.Y, Svendsen C.N., Goodridge H.S. Young bone marrow transplantation preserves learning and memory in old mice. Commun Biol. 2019; 20 (2): 73-9. https://doi.org/10.1038/ s42003-019-0298-5.
  12. Shimbo A., Kosaki Y, Ito I., Watanabe S. Mice lacking hippocampal left-right asymmetry show non-spatial learning deficits. Behav Brain Res. 2018; 336: 156-65. https:// doi.org/10.1016/j.bbr.2017.08.043. Epub 2017 Aug 31.
  13. Swanson E.C., Schleiss M.R. Congenital cytomegalovirus infection: new prospects for prevention and therapy.Pediatr Clin North Am. 2013; 60 (2): 335-49. https://doi. org/10.1016/j.pcl.2012.12.008.
  14. Alarcon A., Martinez-Biarge M, Cabanas F., Hernanz A., Quero J., Garcia-Alix A. Clinical, biochemical, and neuroimaging findings predict long-term neurodeve-lopmental outcome in symptomatic congenital cytomegalovirus infection. J. Pediatr. 2013; 163 (3): 828-34. https://doi. org/10.1016/j.jpeds.2013.03.014.
  15. Murray A.M. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Advances in chronic kidney disease. 2008; 15: 123-32.
  16. Filiano A.J., Kipnis J. Breaking bad blood: P2-microglobulin as a pro-aging factor in blood Nat. Med. 2015; 21 (8): 844-5. https://doi.org/10.1038/nm.3926.
  17. Yang R., Fu S., Zhao L., Zhen B., Ye L., Niu X, Li X., Zhang P, Bai J. Quantitation of circulating GDF-11 and p2-MG in aged patients with age-related impairment in cognitive function. Clin Sci (Lond). 2017; 131 (15): 1895-904. https://doi.org/10.1042/ CS20171028
  18. Załęska-Kocięcka M., Jezierski P., Grabowski M., Kuśmierski K., Dąbrowski M., Piotrowska K., Banaszewski M., Imiela J., Stępińska J. Role of β2-microglobulin in postoperative cognitive decline. Biomark. Med. 2017; 11 (3): 245-53. https://doi.org/10.2217/bmm-2016-0274
  19. Martinez M., Frank A., Hernanz A. Relationship of interleukin-1 beta and beta 2-microglobulin with neuropeptides in cerebrospinal fluid of patients with dementia of the Alzheimer type. J. Neuroimmunol. 1993; 48 (2): 235-40.
  20. Doecke J.D., Laws S.M., Faux N.G., Wilson W., Burnham S.C., Lam C.P, Mondal A., Bedo J., Bush A.I., Brown B., De Ruyck K., Ellis K.A., Fowler C., Gupta V.B., Head R., Macaulay S.L., Pertile K., Rowe C.C., Rembach A., Rodrigues M., Rumble R., Szoeke C., Taddei K., Taddei T, Trounson B., Ames D., Masters C.L., Martins R.N. Alzheimer's Disease Neuroimaging Initiative; Australian Imaging Biomarker and Lifestyle Research Group. Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch Neurol. 2012; 69 (10): 1318-25.
  21. Rembach A., Stingo F.C., Peterson C., Vannucci M., Do K.A., Wilson W.J., Macaulay S.L., Ryan T.M., Martins R.N., Ames D., Masters C.L., Doecke J.D. AIBL Research Group. Bayesian graphical network analyses reveal complex biological interactions specific to Alzheimer's disease. J. Alzheimers Dis. 2015; 44 (3): 917-25. https://doi. org/10.3233/JAD-141497.
  22. Dominici R., Finazzi D., Polito L., Oldoni E., Bugari G., Montanelli A., Scarpini E., Galimberti D., Guaita A. Comparison of p2-microglobulin serum level between Alzheimer's patients, cognitive healthy and mild cognitive impaired individuals. Biomarkers. 2018; 23 (6): 603-8. https://doi.org/10.1080/ 1354750X.2018.1468825.
  23. Chen S.M., Yi Y.L., Zeng D., Tang Y.Y., Kang X., Zhang P, Zou W., Tang X.Q. Hydrogen Sulfide Attenuates p2-Microglobulin-Induced Cognitive Dysfunction: Involving Recovery of Hippocampal Autophagic Flux. ront Behav Neurosci. 2019; 25 (13): 244-9. https://doi.org/10.3389/fn-beh.2019.00244
  24. Boccadoro M., Tarella C., Palumbo A., Argentino C., Triolo S., Dominietto A., Callea V., Lauta V.M., Molica S., Musto P, Marmont F., Gianni A.M., Pileri A. An analysis of which subgroups of multiple myeloma patients, divided according to b(2)-microglobulin and plasma cell labeling index, benefit from high dose vs conventional chemotherapy Haematologica. 1999; 84 (10): 905-10.
  25. Wu Y, Shi L., Feng L., Lv D.L., Zhongguo Shi, Yan Xue, Ye Xue, Za Zhi. Clinical Analysis of Autologous Cytokine-induced Killer Cells Combined with IL-2 for Treating of Elderly Patients with B-cell Malignant Lymphoma). 2016; 24 (3): 738-43. https://doi. org/10.7534/j.issn.1009-2137.2016.03.019.
  26. Kim Y.D., Yim D.H., Eom S.Y., Moon S.I., Park C.H., Kim G.B., Yu S.D., Choi B.S., Park J.D., Kim H. Temporal changes in urinary levels of cadmium, N-acetyl-β-d-glucosaminidase and β2-microglobulin in individuals in a cadmium-contaminated area. Environ Toxicol Pharmacol. 2015; 39 (1): 35-41. https://doi.org/10.10Wj. etap.2014.10.016
  27. Standl E., Balletshofer B., Dahl B., Weichenhain B., Stiegler H., Hermann A., Holle R. Predictors of 10-year macrovascular and overall mortality in patients with NIDDM: the Munich General Practitioner Project. Diabetologia. 1996; 39 (12): 1540-5
  28. Liu Y.S., Wang X., Jiang W.D., Luciani M., Troncone L., Monte F.D. Current and future circulating biomarkers for cardiac amyloidosis. Acta Pharmacol. Sin. 2018; 39 (7): 1133-41. https://doi.org/10.1038/ aps.2018.38
  29. Hoke M., Pernicka E., Niessner A., Goliasch G., Amighi J., Koppensteiner R., Minar E., Mlekusch W., Rumpold H., Wagner O., Schillinger M. Renal function and long-term mortality in patients with asymptomatic carotid atherosclerosis. Thromb Haemost. 2012; 107 (1): 150-7. https://doi. org/10.1160/TH11-06-0383
  30. Rensholt F.F., Ullum H., Katzenstein T.L., Gerstoft J., Ostrowski S.R. Persistent inflammation and endothelial activation in HIV-1 infected patients after 12 years of antiretroviral therapy PLoS One. 2013; 8 (6): e65182. https://doi.org/10.1371/journal. pone.0065182.
  31. Stanga Z., Nock S., Medina-Escobar P,. Nydegger U.E., Risch M., Risch L. Factors other than the glomerular filtration rate that determine the serum beta-2-microglobulinlevel. PLoS One. 2013; 8 (8): e72073. https://doi.org/10.1371/journal. pone.0072073.
  32. Juraschek S.P, Coresh J., Inker L.A., Levey A.S., Kettgen A., Foster M.C., Astor B.C., Eckfeldt J.H., Selvin E. Comparison of serum concentrations of β-trace protein, β2-microglobulin, cystatin C, and creatinine in the US population. Clin. J. Am. Soc. Nephrol. 2013; 8 (4): 584-92. https://doi. org/10.2215/CJN.08700812.
  33. Stakhova T.Iu., Shcherbak A.V., Kozlovskaia L.V., Taranova M.V., Balkarov I.M. Clinical value of the determination of markers for endothelial dysfunction (endothelin-1, microalbuminuria) and tubulointerstitial tissue lesion (β2-microglobulin, monocyte chemotactic protein-1) in hypertensive patients with uric acid metabolic disorders). Ter Arkh. 2014; 86 (6): 45-51.
  34. Leffers H.C.B., Hermansen M.L., Sandholt B., Fuchs A., Sillesen H., K0ber L., Kofoed K.F., Faurschou M., Jacobsen S. Plasma levels of β2-microglobulin are associated with atherosclerosis in patients with systemic lupus erythematosus: a cross-sectional cohort study Lupus. 2018; 27 (9): 1517-23. https://doi. org/10.1177/0961203318784661.
  35. Dong X.M., Cai R., Yang F, Zhang Y.Y., Wang X.G., Fu S.L., Zhang J.R. Predictive value of plasma p2-microglobulin on human body function and senescence. Eur Rev Med. Pharmacol. Sci. 2016; 20 (11): 2350-6.
  36. Keefe J.A., Hwang S.J., Huan T, Men-delson M., Yao C., Courchesne P, Saleh M.A., Madhur M.S., Levy D. Evidence for a Causal Role of the SH2B3-β2M Axis in Blood Pressure. Regulation. Hypertension. 2019; 73 (2): 497-503
  37. Li Y, Zhang X., Li L., Wang X., Chen Z., Wang X., Wang Y., Kang L., Ye Y, Jia J., Zhang G., Yang C., Yuan J., Zhou J., Ge J., Gong H., Zou Y. Mechanical stresses induce paracrine β-2 microglobulin from cardiomyocytes to activate cardiac fibroblasts through epidermal growth factor receptor. Clin. Sci. (Lond). 2018; 132 (16): 1855-74. https://doi.org/10.1042/ CS20180486
  38. Zhang C., Li F., Long T., Li F., Peng L., Xia K., Jing R., Xie Q., Yang T. Beta 2-Microglobulin and the Severity of Coronary Stenosis in Patients With Acute Coronary Syndrome. Heart Lung Circ. 2019; 28 (4): 575-82. https://doi.org/10.10Wj.hlc.2018.02.016.
  39. Foster M.C., Weiner D.E., Bostom A.G., Carpenter M.A., Inker L.A., Jarolim P., Joseph A.A., Kusek J.W., Pesavento T, Pfeffer M.A., Rao M., Solomon S.D., Levey A.S. Filtration Markers, Cardiovascular Disease, Mortality, and Kidney Outcomes in Stable Kidney Transplant Recipients: The FAVORIT Trial. Am. J. Transplant. 2017; 17 (9): 2390-9. https://doi.org/10.1111/ajt.14258.
  40. Kay T.W., Parker J.L., Stephens L.A., Thomas H.E., Allison J. RIP-beta 2-microglobulin transgene expression restores insulitis, but not diabetes, in beta 2-microglobulin null nonobese diabetic mice. J. Immunol. 1996; 157 (8): 3688-93.
  41. Ekrikpo U.E., Effa E.E., Akpan E.E., Obot A.S., Kadiri S. Clinical Utility of Urinary P2-Microglobulin in Detection of Early Nephropathy in African Diabetes Mellitus Patients. Int. J. Nephrol. 2017; 40 (9): 3171-8. https://doi.org/10.1155/2017/4093171.
  42. Colombo M., Looker H.C., Farran B., Hess S., Groop L., Palmer C.N.A., Brosnan M.J., Dalton R.N., Wong M., Turner C., Ahlqvist E., Dunger D., Agakov F., Durrington P., Livingstone S., Betteridge J., McKeigue P.M., Colhoun H.M. Serum kidney injury molecule 1 and β2-microglobulin perform as well as larger biomarker panels for prediction of rapid decline in renal function in type 2 diabetes. SUMMIT Investigators. Diabetologia. 2019; 62 (1): 156-68. https://doi. org/10.1007/s00125-018-4741-9.
  43. Azenabor A., Ogbera A.O., Adejumo N.E., Adejare A.O. Acute phase reactant dynamics and incidence of microvascular dysfunctions in type 2 diabetes mellitus. J. Res. Med. Sci. 2011; 16 (10): 1298-305.
  44. Javadi S., Asri-Rezaei S., Allahverdizadeh M. Interrelationship of beta-2 microglobulin, blood urea nitrogen and creatinine in streptozotocin-induced diabetes mellitus in rabbits Vet Res Forum. 2014; 5 (1): 7-11.
  45. Li L., Dong M., Wang X.G. The Implication and Significance of Beta 2 Microglobulin: A Conservative Multifunctional Regulator, Chin. Med. J. (Engl). 2016; 129 (4): 448-55. https://doi.org/10.4103/0366-6999.176084.
  46. Shi C.1., Zhu Y, Su Y, Chung L.W., Cheng T. Beta2-microglobulin: emerging as a promising cancer therapeutic target. Drug Discov. Today. 2009; 14 (1-2): 25-30. https:// doi.org/10.1016/j.drudis.2008.11.001.
  47. Sliker B.H., Goetz B.T., Peters H.L., Poelaert B.J., Borgstahl G.E.O., Solheim J.C. Beta 2-microglobulin regulates amyloid precursor-like protein 2 expression and the migration of pancreatic cancer cells. Cancer Biol Ther. 2019; 20 (6): 931-40. https:// doi.org/10.1080/15384047.2019.1580414.
  48. Chai D., Li K., Du H., Yang S., Yang R., Xu Y, Lian X. β2-microglobulin has a different regulatory molecular mechanism between ER+ and ER- breast cancer with HER2. BMC Cancer. 2019; 19 (1): 22331. https://doi. org/10.1186/s12885-019-5410-1.
  49. Sun W., Gui L., Zuo X., Zhang L., Zhou D., Duan X., Ren W., Xu G. Human epithelialtype ovarian tumour marker beta-2-microglobulin is regulated by the TGF-β signaling pathway. J. Transl. Med. 2016; 14: 75-83. https://doi.org/10.1186/s12967-016-0832-x
  50. Yusuke Kanemasa Tatsu, Shimoyama Yuki, Sasaki Miho, Tamura Takeshi, Sawada Yasushi, Omuro Tsunekazu Hishima. Beta-2 microglobulin as a significant prognostic factor and a new risk model for patients with diffuse large B-cell lymphoma. Hematological Oncolog, 2017. https://doi. org/10.1002/hon.2312.
  51. Lucarelli G., Ditonno P., Bettocchi C., Vavallo A., Rutigliano M., Galleggiante V, Larocca A.M., Castellano G., Gesualdo L., Grandaliano G., Selvaggi F.P., Battaglia M. Diagnostic and prognostic role of preoperative circulating Ca 15-3, CA 125, and beta-2 microglobulin in renal cell carcinoma. Dis. Markers. 2014; 68: 9795-8. https://doi.org/10.1155/2014/689795. Epub 2014 Feb 17
  52. Hinterleitner C., Pecher A.C., KreiBelmeier K.P., Budde U., Kanz L., Kopp H.G., Jaschonek K. Disease progression and defects in primary hemostasis as major cause of bleeding in multiple myeloma. Eur. J. Haematol. 2020; 104 (1): 26-35. https://doi. org/10.1111/ejh.13331.
  53. Prizment A.E., Linabery A.M., Lutsey P.L., Selvin E., Nelson H.H., Folsom A.R., Church T.R., Drake C.G., Platz E.A., Joshu C. Circulating Beta-2 Microglobulin and Risk of Cancer: The Atherosclerosis Risk in Communities Study (ARIC).Cancer Epidemiol. Biomarkers Prev. 2016; 25 (4): 657-64. https:// doi.org/10.1158/1055-9965.EPI-15-0849.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies