Induction to alternative splicing of bace1 gene with sodium butyrate and butein in SH SY5Y cell line and identification of resulting isoform profile

BACE1 enzyme (beta-site amyloid precursor protein enzyme 1) has a highly important role in treatment for Alzheimer Disease which is in first place within group of neurodegenerative disease. The enzyme is responsible for production β-amyloid which is hallmark of Alzheimer's Disease. It is reported that the enzyme has several isoform in different tissues apart from full-lenght active form in brain tissue. Also it is shown that increase in amount of these alternatively spliced isoforms reduces amount of β-amyloid which has important function in Alzheimer's Disease. In this study, it has been examined effect of sodium butyrate and butein known as histone deacetylase inhibitor on alternative splicing of the BACE1 enzyme known importance in Alzheimer's Disease. It has evaluated effect of sodium butyrate (1 mM and 5 mM) and butein (2 µM and 10 µM) treated to SH-SY5Y cell on expression of alternatively spliced isoforms by Real-Time PCR. According to Mann-Whitney U test, it has not found significant differences between dozes of both sodium butyrate and butein (p>0.05) Both 1 mM and 5 mM concentration of sodium butyrate has increased in expression of BACE1501 compared to control group. While 1mM sodium butyrate has decreased in expression of BACE1/457 and BACE1/432, 5 Mm sodium butyrate has increased in BACE1/457 and BACE1/432. Both 2 µM and 10 µM butein has increased in expression of BACE1/501 compared to control group. Whereas 2 µM butein has increased in expression of BACE1/457 a little bit, 10 µM butein has tripled expression of BACE1/457. While 2 µM butein has no change on BACE1/432, 10 µM butein has approximately doubled expression of BACE1/432. As a result, it has been determined that HDAC inhibitors which we used selectively didn't cause effect which we estimated as significant changes in expression level on BACE1 isoforms.