Date

2022-2

Author

Akyıldız, Zeynep Eda

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Boron is the basic element of borax mineral reserves which a significant amount is found in Turkey. Elemental boron which has wide use in industrial areas recently started to be used in the development of new products in the pharmaceutical industry. However, despite the widespread use in industry and increasing use in health sciences, the molecular mechanism of its effect is still unknown. Previous microarray studies performed in our laboratory and the analysis of the results have shown that boric acid has an inhibitory effect on the steroid metabolism pathway. According to the analysis, the expressions of several genes in the pathway were found to be changed significantly with boric acid treatment at IC50 concentration. In this study, in order to confirm the microarray results and to search for the possible role of boric acid in cholesterol synthesis, the gene and protein expressions of some enzymes in this pathway were investigated in the HepG2 cell line. The genes were selected according to their expressions and their roles in the pathway. Expressions of genes which are coding for 7- dehydrocholesterol reductase (DHCR7), Methylsterol Monooxygenase 1 (MSMO1), Emopamil Binding Protein (sterol isomerase) (EBP), Farnesyl-diphosphate Farnesyltransferase 1 (FDFT1), Lanosterol Synthase (2,3-oxidosqualene-lanosterol cyclase) (LSS), Sterol-C5-desaturase (SC5D), and Squalene Epoxidase (SQLE) were examined at IC10, IC25, and IC50 boric acid concentrations. No significant change was observed in MSMO1 gene expression at all three concentrations of boric acid. On the other hand, significant changes were seen in all DHCR7, SQLE, EBP, and LSS gene expressions. In LSS, whose protein levels were also examined, a significant decrease was observed with IC10 treatment, while no significant increase or decrease was observed in either IC50 or IC25 concentrations. However, in SQLE protein expression a significant decrease was observed in all treatment groups. Contrary to our expectations, the expression of the 7-dehydrocholesterol reductase (DHCR7) gene, which catalyzes the final step in the cholesterol pathway increased significantly at IC25 treated cells. In light of the data obtained, a more detailed study of the steroid pathway enzymes at the level of both protein and gene expression should be done in order to understand the action mechanism and the possible use of boric acid as a drug in cholesterol metabolism.

Subject Keywords

Boric acid, 7-dehydrocholesterol reductase, Steroid metabolism, HepG2 cell line, Cholesterol metabolism

URI

https://hdl.handle.net/11511/96064

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Graduate School of Natural and Applied Sciences, Thesis