Features of Bcl2 and p53 proteins synthesis in pancreatic islets of normotensive and hypertensive rats with streptozotocin-induced diabetes

Abstract

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.