Features of Bcl2 and p53 proteins synthesis in pancreatic islets of normotensive and hypertensive rats with streptozotocin-induced diabetes
DOI:
https://doi.org/10.14739/2310-1237.2019.3.188846Keywords:
essential hypertension, diabetes mellitus, pancreatic islets, apoptosisAbstract
In our previous studies it was established that the remodeling of pancreatic islets with decreasing β-cell population density is formed in hypertensive SHR rats. The imbalance between the synthesis of proapoptotic and antiapoptotic factors may be one of the possible causes of disturbed formation of the endocrinocyte population in the pancreas.
The aim of the research was to study the parameters of Bcl2 and p53 proteins synthesis in pancreatic islets in normotensive and hypertensive rats in the streptozotocin-induced diabetes mellitus development.
Materials and methods. The study was performed on 30 normotensive male Wistar rats (systolic BP=105.0 ±1.1 mm Hg) and 25 hypertensive SHR rats (systolic BP=155.7 ±0.9 mm Hg) with fasting normoglycemia (4.73 ± 0.10 mmol/l). Bcl2 and p53 proteins were detected in histological pancreas sections by immunofluorescence method. The relative area of Bcl2- and p53-immunopositive material, concentration of proteins in endocrinocytes, their content in the islets and apoptosis index p53/Bcl2 were analyzed in pancreatic islands.
Results. The area of relative immunofluorescence to the Bcl2 protein was 2 times less, and the protein content was 3 times lower in pancreatic islets of hypertensive rats (SHR) compared with normotensive Wistar rats. At the same time, no statistical differences in the area of the immunopositive material to the p53 protein and its content in the islets between the experimental groups were revealed. The development of streptozotocin-induced diabetes in Wistar rats was accompanied by approximately 2-fold decrease in the Bcl2 protein expression in pancreatic islets, a significant increase in the specific content of p53 protein and a 3.8-fold increase in the apoptosis index of p53/Bcl2. In pancreatic islets of SHR rats, diabetes mellitus development was accompanied by 2-fold increase in the specific content of the proapoptotic protein p53 without the reduction of the antiapoptotic protein Bcl2 synthesis. At the same time, the p53/Bcl2 apoptosis index in SHR rats remained statistically higher than in Wistar rats.
Conclusions. Endocrine cells of pancreatic islets of SHR rats are characterized by the prevalence of proapoptotic protein p53 expression as compared with Wistar line normotensive rats. The development of streptozotocin diabetes in Wistar rats leads to a significant decrease in the number of endocrinocytes synthesizing the antiapoptotic protein Bcl2. At the same time, an increase in the synthesis of the proapoptotic protein p53 in endocrinocytes in diabetes is observed both in normotensive and in hypertensive rats.
References
Yoon, S. S., Carroll, M. D., & Fryar, C. D. (2015). Hypertension Prevalence and Control among Adults: United States, 2011-2014. NCHS Data Brief, 220, 1-8.
Seferovic, P. M., Petrie, M. C., Filippatos, G. S., Anker, S. D., Rosano, G., Bauersachs, J., . . . McMurray, J. J. V. (2018). Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology. European Journal of Heart Failure, 20(5), 853-872. https://doi.org/10.1002/ejhf.1170
Wou, C., Unwin, N., Huang, Y. D., & Roglic, G. (2019). Implications of the growing burden of diabetes for premature cardiovascular disease mortality and the attainment of the Sustainable Development Goal target 3.4. Cardiovascular Diagnosis and Therapy, 9(2), 140-149. https://doi.org/10.21037/cdt.2018.09.04
Gancheva, О. V., Kolesnik, Yu. М., Аbramova, Т. V., Samoylenko, N. Yu., & Abramov, A. V. (2013). Metabolic disturbances in hypertensive SHR rats. Klinichna farmatsiia, 17(4), 56-58.
Abramova, T. V. (2016). The distribution of the islets of Langerhans in pancreas of euglycemic spontaneously hypertensive rats. Pathologia(1), 19-21. https://doi.org/10.14739/2310-1237.2016.1.72359
Abramova, T. V., & Kolesnyk, Y. M. (2016). The features of beta-cells organization in the pancreas of spontaneously hypertensive rat (SHR). Pathologia(3), 4-8. https://doi.org/10.14739/2310-1237.2016.3.86931
Abramova, T. V., & Kolesnyk, Y. M. (2017). Osobennosti organizatsii populyatsii al'fa-kletok v podzheludochnoi zheleze u krys so spontannoi gipertenzii (SHR) [Features of the alpha-cell population organization in pancreas of spontaneously hypertensive rats (SHR)]. Pathologia(2), 124-128. [in Russian]. https://doi.org/10.14739/2310-1237.2017.2.109249
Abramova, T. V., Kolesnik, Yu. M., & Ivanenko, T. V. (2017). Funktsional'noe sostoyanie -kletok podzheludochnoi zhelezy u krys so spontannoi gipertenzii (SHR) pri eksperimental'nom diabete [Functional status of -cells in pancreas of spontaneously hypertensive rats with experimental diabetes]. Aktualni Problemy Suchasnoi Medytsyny, 4 (60), 8-12. [in Russian].
Abramova, T., Kolesnik, Y., & Ivanenko, T. (2018). Kolichestvennyye izmeneniya populyatsii endokrinotsitov podzheludochnoy zhelezy u krys linii SHR na fone razvitiya streptozototsin-indutsirovannogo diabeta [Quantitative changes in the pancreatic endocrinocyte population in SHR rats against the background of the development of streptozotocin-induced diabetes]. Klinichna ta eksperymentalna patolohiia, 4(66), 8-14. [in Russian]. https://doi.org/10.24061/1727-4338XVE466.2018.181
Plesner, A., ten Holder, J. T., & Verchere, C. B. (2014). Islet Remodeling in Female Mice with Spontaneous Autoimmune and Streptozotocin-Induced Diabetes. Plos One, 9(8). https://doi.org/10.1371/journal.pone.0102843
Li, Z., Karlsson, F. A., & Sandler, S. (2000). Islet loss and alpha cell expansion in type 1 diabetes induced by multiple low-dose streptozotocin administration in mice. Journal of Endocrinology, 165(1), 93-99. https://doi.org/10.1677/joe.0.1650093
Zhang, Y., Zhang, Y., Bone, R. N., Cui, W., Peng, J. B., Siegal, G. P., … Wu, H. (2012). Regeneration of pancreatic non-β endocrine cells in adult mice following a single diabetes-inducing dose of streptozotocin. PloS one, 7(5), e36675. https://doi.org/10.1371/journal.pone.0036675
Ivanenko, T. V., Abramov, A. V., Kolesnik, Yu. M., Vasilenko, G. V. (2011). Endokrinnyi status i uroven' ekspressii belkov Bcl-2 i p53 v pankreaticheskikh ostrovkakh u krys s eksperimental'nym sakharnym diabetom [Endocrine status and expression level of Bcl-2 and p53 proteins in pancreatic islets in rats with experimental diabetes mellitus]. Pathologia, 8(2), 18-20. [in Russian].
Ivanenko, T. V., Kolesnyk, Yu. M., & Abramova T. V. (2017). Analiz endokrynnoho statusu ta rivnia ekspresii bilkiv apoptozu i proliferatsii v pankreatychnykh ostrivtsiakh shchuriv z eksperymentalnym tsukrovym diabetom pislia zakinchennia pereryvchastykh hipoksychnykh trenuvan [Analysis of endocrine status and pro-apoptotic protein expression and proliferation in pancreatic islets in rats with experimental diabetes mellitus after intermittent hypoxic training]. Patolohiia, reabilitatsiia, adaptatsiia, 15(2), 87-93. [in Ukrainian].
Edlich, F. (2018). BCL-2 proteins and apoptosis: Recent insights and unknowns. Biochemical and Biophysical Research Communications, 500(1), 26-34. https://doi.org/10.1016/j.bbrc.2017.06.190
Lee, S. C., & Pervaiz, S. (2007). Apoptosis in the pathophysiology of diabetes mellitus. International Journal of Biochemistry & Cell Biology, 39(3), 497-504. https://doi.org/10.1016/j.biocel.2006.09.007
Hotchkiss, R. S., Strasser, A., McDunn, J. E., & Swanson, P. E. (2009). Mechanisms of Disease Cell Death. New England Journal of Medicine, 361(16), 1570-1583. https://doi.org/10.1056/NEJMra0901217
Saldeen, J. (2000). Cytokines induce both necrosis and apoptosis via a common bcl-2-inhibitable pathway in rat insulin-producing cells. Endocrinology, 141(6), 2003-2010. https://doi.org/10.1210/en.141.6.2003
Kung, C. P., & Murphy, M. E. (2016). The role of the p53 tumor suppressor in metabolism and diabetes. Journal of Endocrinology, 231(2), R61-R75. https://doi.org/10.1530/joe-16-0324
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