Tag Archives: CYP27A1
Cholecalciferol hydroxylation in rat hepatocytes under the influence of prednisolone
A. V. Khomenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: annavic@ukr.net
Glucocorticoid therapy is accompanied by development of processes typical of steroid osteoporosis. Indirect effects of glucocorticoids on the bone tissue are due to changes in mineral metabolism, which is regulated by vitamin D3. In this connection, we studied the influence of prednisolone on cholecalciferol metabolism. The study has shown that prednisolone action causes impairment of cholecalciferol metabolism in hepatocytes due to inhibiting vitamin D3 25-hydroxylase activity. Microsomal (CYP2R1) and mitochondrial (CYP27A1) isoenzymes of vitamin D3 25-hydroxylase were found to function at different concentrations of the substrate. The relative protein contents of the isoenzymes greatly differed in the liver with the prevalence of CYP27A1 over CYP2R1. Prednisolone administration resulted in the lowering of both mitochondrial and microsomal isoenzymes of vitamin D3 25-hydroxylase. The inhibition of vitamin D3 25-hydroxylating system in hepatocytes contributed to a significant reduction in blood serum 25OHD3.
Vitamin D(3) availability and functional activity of peripheral blood phagocytes in experimental type 1 diabetes
D. О. Labudzynskyi, І. О. Shymanskyy, V. М. Riasnyi, М. М. Veliky
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: konsument3@gmail.com
The study was devoted to identifying the relation between vitamin D3 availability (assessed by the level of circulatory 25OHD3), content of vitamin D3 25-hydroxylase isozymes CYP27A1 and CYP2R1 in hepatic tissue and functional activity of peripheral blood phagocytes in mice with experimental type 1 diabetes. It has been shown that diabetes is accompanied by the development of vitamin D3-deficiency which is characterized by decreased 25OHD3 content in blood serum and determined by changes in tissue expression of the major isoforms of vitamin D3 25-hydroxylase. The level of hepatic CYP27A1 was revealed to be markedly reduced with a concurrent significant augmentation of CYP2R1. Cholecalciferol administration resulted in normalization of tissue levels of both isoforms of vitamin D3 25-hydroxylase and blood serum 25OHD3 content. Diabetes-associated vitamin D3 deficiency correlated with a decrease in phagocytic activity of granulocytes and monocytes, and their ability to produce antibacterial biooxidants such as reactive oxygen and nitrogen forms. Vitamin D3 efficacy to attenuate these abnormalities of immune function was established, indicating an important immunoregulatory role of cholecalciferol in the phagocytic mechanism of antigens elimination implemented by granulocytes and monocytes.