ACTIVITY OF CATHEPSINS B, L AND H IN BLOOD PLASMA IN PATIENTS WITH CHRONIC DIFFUSE LIVER DISEASES

Authors

  • H. V. Dolgikh DNIPROPETROVSK MEDICAL ACADEMY OF THE MINISTRY OF HEALTH OF UKRAINE
  • H. S. Maslak DNIPROPETROVSK MEDICAL ACADEMY OF THE MINISTRY OF HEALTH OF UKRAINE
  • V. I. Didenko INSTITUTE OF GASTROENTEROLOGY OF THE NAMS OF UKRAINE, DNIPRO
  • I. A. Klenina INSTITUTE OF GASTROENTEROLOGY OF THE NAMS OF UKRAINE, DNIPRO
  • O. E. Abraimova DNIPROPETROVSK MEDICAL ACADEMY OF THE MINISTRY OF HEALTH OF UKRAINE

DOI:

https://doi.org/10.11603/mcch.2410-681X.2020.v.i1.11052

Keywords:

cathepsin B, cathepsin H, cathepsin L, α1-antitrypsin, α2-macroglobulin, chronic diffuse liver diseases, serological fibrosis biomarkers

Abstract

Introduction. Plasma markers are widely used along with trepanobiopsy to diagnose the histological stages of chronic diffuse liver diseases.

The aim of the study – to determine the activity of cysteine cathepsins B, L, H and the content of proteolysis inhibitors α1-antitrinsin and α2-macroglobulin in the blood plasma of patients with chronic diffuse liver diseases of non-viral etiology.

Research Methods. The object of research is the blood plasma of patients with chronic diffuse liver diseases (n=51) aged 28–60 years hospitalized in the Department of Liver and Pancreas Diseases of the Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine. The control group consisted of healthy volunteers (n = 15) aged from 25 to 52 years. The activity of cathepsins B, L and H were determined relatively to N-α-benzoyl-DL-arginine-4-nitroanilide hydrochloride, to azocasein and to oxytocin, respectively. The solution of N-α-benzoyl-DL-arginine-4-nitroanilide hydrochloride was used as a substrate for determination the content of inhibitors in human blood plasma.

Results and Discussion. Compared with the group of practically healthy donors, statistically significant differences were recorded in: patients with steatohepatitis, the activity of cathepsin B increases by 26.7 %, and the level of α2-macroglobulin decreases by 30.7 %; in patients with chronic viral hepatitis with transition to cirrhosis, the activity of cathepsin B increases by 43.8 %, the activity level of cathepsin H decreases by 35 %, and the content of α2-macroglobulin, on the contrary, increases by 71.5 %; in the group of patients with steatohepatosis, the activity of cathepsin L and H decreases by 22.1 % and 25 %, respectively, and the concentration of α1-antitrypsin increases by 19.3 %.

Conclusions. Determination of the content of inhibitors in conjunction with the activity of cysteine cathepsin in blood plasma can be proposed as non-invasive markers for chronic diffuse liver diseases of non-viral etiology.

References

Didenko, V.І. (2013). Sovremennye metody opredeleniya fibroza pecheny [Modern methods for de­termining liver fibrosis]. Chelovek i lekarstvo. Biome­dytsynskaya khimiya – Human and Medicine. Biomedical Chemistry, 13 (29), 84-89 [in Russian].

Didenko,V.І., Klenіna, І.A., & Oshmyanska, N.Y. (2014). Morfologicheskaya i biokhimicheskaya otsenka progressyrovaniya khronicheskogo gepatita assotsyyro­vannogo s virusom “C” [Morphological and biochemical assessment of the progression of chronic hepatitis associated with the virus “C”]. Hastroenterolohiia: zbirnyk naukovykh statei – Gastroenterology: Collection of Scientific Articles, 2 (52), 37-41 [in Russian].

Nallagangula, K.S., Nagaraj, S. K., Venkataswa­my, L., & Chandrappa, M. (2017). Liver fibrosis: a compilation on the biomarkers status and their significance during disease progression. Future Sci., OA, 4 (1).

DОІ: 10.4155 / fsoa-2017-0083 DOI: https://doi.org/10.1002/cssc.201701266

Chundru, S., Kalb, B., Arif-Tiwari, H., Sharma, P., Costello, J., & Martin, C.R. (2014). MRI of diffuse liver disease: characteristics of acute and chronic diseases. Diagnostic and Interventional Radiology, 20 (3), 200-208. DOI: 10.5152/ dir.2014.13170 DOI: https://doi.org/10.5152/dir.2014.13170

Fiore, V., Hagood, J., & Barker, Т. (2018). αvβ3 Integrin drives fibroblast contraction and strain stiffening of soft provisional matrix during progressive fibrosis. JCI Insight, 3 (20), 97597. DOI: 10.1172/jci.insight.97597 DOI: https://doi.org/10.1172/jci.insight.97597

Manchanda, M., Das, P., Gahlot, G.P., Singh, R., Roeb, E., Roderfeld, M., … Chauhan, S.S. (2017). Cathepsin L and B as рotential markers for liver fibrosis: insights from patients and experimental models. Clinical and Translational Gastroenterology, 8 (6), 99. DOI: 10.1038/ctg.2017.25

Yang, Z., Liu, Y., Qin, L., Wu, P., Xia, Z., Luo, M., … Han, Y. (2017). Cathepsin H – mediated degradation of HDAC4 for matrix metalloproteinase expression in hepatic stellate cells: implications of epigenetic suppression of matrix metalloproteinases in fibrosis through stabilization of class IIa histone deacetylases. The American Journal of Pathology, 187 (4), 781-797. DOI: 10.1016/j.ajpath.2016.12.001 DOI: https://doi.org/10.1016/j.ajpath.2016.12.001

Tan, G., Liu, Q., Tang, X., Kang, T., Li, Y., Lu, J., … Tang, F. (2016). Diagnostic values of serum cathepsin B and D in patients with nasopharyngeal carcinoma. BMC Cancer, 16, 241. DOI: 10.1186/s12885-016-2283-4 DOI: https://doi.org/10.1186/s12885-016-2283-4

Liu, W.L., Liu, D., Cheng, K., Liu, Y.J., Xing, S., Chi, P.D., … Zhang, G. (2016). Evaluating the diagnostic and prognostic value of circulating cathepsin S in gastric cancer. Oncotarget, 7 (19), 28124-28138. DOI: 10.18632/oncotarget.8582. DOI: https://doi.org/10.18632/oncotarget.8582

Ellen, L., Mitchell, & Khan, Z. (2017). Liver disease in alpha-1 antitrypsin deficiency: Current ap­proaches and future directions. Current Pathobiology Reports, 5 (3), 243-252. DOI: 10.1007/s40139-017-0147-5 DOI: https://doi.org/10.1007/s40139-017-0147-5

Fairbanks, K.D., & Tavill, A.S. (2008). Liver disease in alpha 1-antitrypsin deficiency: a review. American Journal of Gastroenterology, 103 (8), 2136-2141. DOI: 10.1111/j.1572-0241.2008.01955.x. DOI: https://doi.org/10.1111/j.1572-0241.2008.01955.x

Bradshaw, R.S., Ericsson, L.H., & Walsh, K.A. (1969). The amino acid sequence of bovine carboxy­peptidase. Proceedings of the National Academy of Sciences, 63 (4), 1389-1394. DOI: https://doi.org/10.1073/pnas.63.4.1389

Bradford, M.M. (1976). A rapid and sensitive method for the quantification of microgramme quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72, 248-254. DOI: https://doi.org/10.1016/0003-2697(76)90527-3

Schlisterman, E.F., Perkins, N.J., & Liu A. (2005). Optimal cut-point and it's corresponding youden index to discriminate individuals using pooled blood samples. Epidemiology, 16, 73-81. DOI: https://doi.org/10.1097/01.ede.0000147512.81966.ba

Dolgikh, A.V., Netronina, O.V., Maslak, A.S., & Abraymova, O.V. (2018). Genetichesky determinirovanye osobenosti vvliyaniya molekulyarnoy struktury otdelnykh izoform fibronektna na patogenicheskoy znachymye protsesy metabolizma v organizme (obzor literatury) [Genetically determined features of the influence of the molecular structure of individual fibronectin isoforms on pathogenically significant metabolic processes in the body (literature review)]. Laboratornaya diagnostika. Vostoch­naya Yevropa – Laboratory Diagnostics. Eastern Europe, 7 (3), 342-359 [in Russian].

Turk, V., Stoka, V., Vasiljeva, O., Renko, M., Sun, T., Turk, B., & Turk, D. (2012). Cysteine cathepsins: From structure, function and regulation to new fron­tier. Biochimica et Biophysica Acta, 1824 (1), 68-88.

DOI: 10.1016/j.bbapap.2011.10.002 DOI: https://doi.org/10.1016/j.bbapap.2011.10.002

Hernandez-Gea, V., & Friedman, S.L. (2011). Pathogenesis of liver fibrosis. Annual Review of Path­ology: Mechanisms of Disease, 6, 425-456. DOI: 10.1146/annurev-pathol-011110-130246. DOI: https://doi.org/10.1146/annurev-pathol-011110-130246

Novinec, М., Lenarčič, В., & Turk, В. (2014). Cysteine cathepsin activity regulation by glycosami­noglycans. BioMed. Research International, 2, 309718-309719. DOI: 10.1155/2014/309718 DOI: https://doi.org/10.1155/2014/309718

López-Guisa, J.M., Cai, X., Collins, S.J., Yama­guchi, I., Okamura, D.M., Bugge, T.H., … Eddy, A.A. (2012). Mannose receptor 2 attenuates renal fibrosis. Journal of the American Society of Nephrology, 23 (2), 236-251. DOI: 10.1681/ASN.2011030310 DOI: https://doi.org/10.1681/ASN.2011030310

Manchanda, M., Das, P., Gahlot, G.P., Singh, R., Roeb, E., Roderfeld, M., … Chauhan, S.S. (2017). Cathepsin L and B as рotential markers for liver fibrosis: insights from patients and experimental models. Cli­nical and Translational Gastroenterology, 8 (6), 99.

DOI: 10.1038/ctg.2017.25 DOI: https://doi.org/10.1038/ctg.2017.25

Teckman, J.H., & Blomenkamp K.S. (2017). Pathophysiology of alpha-1 antitrypsin deficiency liver disease. Alpha-1 antitrypsin deficiency, methods and protocols. Part of the Methods in Molecular Biology, 1639, 1-8. DOI:https://doi.org/10.1007/978-1-4939-7163-3_1 DOI: https://doi.org/10.1007/978-1-4939-7163-3_1

Ho, A.S., Cheng, C.C., Lee, S.C., Liu, M.L., Lee, J.Y., Wang, W.M., & Wang, С.С. (2010). Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI. Journal of Biomedical Science, 17 (1). DOI: 10.1186/1423-0127-17-58 DOI: https://doi.org/10.1186/1423-0127-17-58

Maslak, A.S., Kostyuk, O.V., Masheyko, I.V., & Brazaluk, A.Z. (2013). Soderzhanie α-1-kislogo gliko­proteina i syalovykh kislot v biologicheskikh zhidkostyakh u bolnykh s khronicheskimi meloproliferativnymi zabo­levaniyami [The content of α-1-acid glycoprotein and sialic acids in biological fluids in patients with chronic myelo­proliferative disease]. Zhurnal Grodnenskogo gosudarst­vennogo meditsinskogo universiteta – Journal of Grodno State Medical University, 41 (1), 39-42. [in Russian].

Maslak, A.S. (2013). Stepen razvetvlennosti N-glikanov belkov plazmy u patsiyentov s khronicheskim limfoleykozom na raznykh stadiyakh lecheniya [Degree of branching of N-glycans of plasma proteins in patients with chronic lymphocytic leukemia at different stages of treatment]. Zhurnal Grodnenskogo gosudarstvennogo mediczinskogo universiteta – Journal of Grodno State Medical University, 44 (4), 97-101 [in Russian].

Published

2020-04-28

How to Cite

Dolgikh, H. V., Maslak, H. S., Didenko, V. I., Klenina, I. A., & Abraimova, O. E. (2020). ACTIVITY OF CATHEPSINS B, L AND H IN BLOOD PLASMA IN PATIENTS WITH CHRONIC DIFFUSE LIVER DISEASES. Medical and Clinical Chemistry, (1), 23–35. https://doi.org/10.11603/mcch.2410-681X.2020.v.i1.11052

Issue

Section

ORIGINAL INVESTIGATIONS