RGD Reference Report - Cellular function of RhoGDI-alpha mediates the cycling of Rac1 and the regulation of pancreatic beta cell death. - Rat Genome Database
Mycophenolic acid (MPA) is an immunosuppressive agent that is widely used in clinical therapy, including pancreas and islet transplantation. Previously, we showed that MPA induces significant apoptosis of insulin-secreting cells by downregulating RhoGDI-alpha and increasing JNK expression. In this study, we investigated Rac1 directly associated with RhoGDI-alpha during MPA-induced apoptosis in INS-1E cells (an insulin-secreting cell line). Cells were treated with MPA for 24 and 36 hours. Immunoprecipitation was used to examine physical interactions between RhoGDI-alpha and Rac1. Activation and immunoprecipitation assays showed expressions of Rac1 and RhoGDI-alpha to be directly correlated. Rac1 binding to RhoGDI-alpha decreased after MPA treatment, and Rac1 was induced and subsequently activated by MPA. We concluded that this novel RhoGDI-alpha/Rac1/JNK pathway induced apoptosis of transplanted islet cells after MPA treatment.