title: Cellular function of RhoGDI-α mediates the cycling of Rac1 and the regulation of pancreatic beta cell death.
abstract: 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-α and increasing JNK expression. In this study, we investigated Rac1 directly associated with RhoGDI-α 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-α and Rac1. Activation and immunoprecipitation assays showed expressions of Rac1 and RhoGDI-α to be directly correlated. Rac1 binding to RhoGDI-α decreased after MPA treatment, and Rac1 was induced and subsequently activated by MPA. We concluded that this novel RhoGDI-α/Rac1/JNK pathway induced apoptosis of transplanted islet cells after MPA treatment.
authors.affiliation: The Research Institute for Transplantation, Yonsei University Health System, Seoul, South Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Cho
authors.forename: K H
authors.initials: KH
authors.lastname: Huh
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Park
authors.forename: J H
authors.initials: JH
authors.lastname: Do
authors.forename: D J
authors.initials: DJ
authors.lastname: Joo
authors.forename: M S
authors.initials: MS
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D047468:Immunoprecipitation; D007166:Immunosuppressive Agents / Q000633:toxicity*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D009173:Mycophenolic Acid / Q000633:toxicity*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: D020730:Guanine Nucleotide Dissociation Inhibitors; D007166:Immunosuppressive Agents; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D009173:Mycophenolic Acid