Mechanism study of the induction of cell death by selenoprotein P in pancreatic beta cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26850089
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Food science
• Research Institution: Doshisha University
• Principal Investigator: Takabe Wakako 同志社大学, 生命医科学部, 准教授 (00436594)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 糖尿病 / 細胞死

Outline of Final Research Achievements

Blood levels of selenoprotein P (SeP) are elevated in patients with type 2 diabetes. Also concentration of SeP correlated with insulin resistance. In this study, we aimed to clarify how excess selenoprotein P (SeP) induces disorder of MIN6 cells, a model of pancreatic beta cells. SeP induced cell death in dose-dependent manner in MIN6 cells. SeP induced caspase-3 activation and pan caspase inhibitor z-VAD-FMK rescued SeP-induced cell death suggested that excess SeP induces apoptosis in MIN6 cells. Several reports were shown the relationship between ER-stress and diabetes, in the next series of experiments we focused on contribution of ER-stress on SeP-dependent apoptosis. Marker proteins of endoplasmic reticulum (ER) stress such as CHOP and GRP78 were also induced by SeP. SeP-induced cell death were abolished by 4-Phenylbutyric acid, an inhibitor of ER stress. These result suggested that excess amount of SeP induced apoptosis via ER stress in pancreatic beta cells.

Free Research Field

分子生物学