title: PRMT3: new binding molecule to RhoGDI-α during mycophenolic acid-induced β-cell death.
abstract: Mycophenolic acid (MPA)-induced beta cell toxicity limits islet graft survival. However, the signal transduction mechanisms underlying MPA-induced β-cell toxicity have not been fully elucidated. Previously, we showed that MPA-induced pancreatic β-cell apoptosis proceeds via RhoGDI-α down-regulation linked to Rac1 activation. In the present study, we investigated factors affecting RhoGDI-α during MPA-induced β-cell apoptosis. The presence of RhoGDI-α-related protein was determined with the use of yeast 2-hybrid (Y2H) analysis. Y2H screening of RhoGDI-α was performed in yeast PBN204 strain containing 3 reporters (URA3, lacZ, and ADE2) under the control of different GAL promoters. INS-1E cells (an insulin-secreting pancreatic β-cell line) were treated with MPA for 12, 24, and 36 hours. Eighty-three real positives were obtained by Y2H analysis, and of these, arginine N-methyltransferase 3 (PRMT3) protein interacted with RhoGDI-α in INS-1E cells. PRMT3 gene expressions and its protein levels were significantly decreased during MPA-induced apoptosis. In summary, PRMT3 and RhoGDI-α were found to interact in INS-1E cells. Furthermore, MPA was found to regulate this interaction in INS-1E cells by down-regulating the gene expression of PRMT3. These findings suggest that control of the interaction between PRMT3 and RhoGDI-α could be used to prevent MPA-induced β-cell death.
authors.affiliation: Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea.
authors.forename: K H
authors.initials: KH
authors.lastname: Huh
authors.affiliation: Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea; Department of Internal Medicine, Severance Hospital, Yonsei University Health System, Seoul, Korea.
authors.forename: B S
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea.
authors.forename: D J
authors.initials: DJ
authors.lastname: Joo
authors.affiliation: Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea.
authors.forename: M S
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea. Electronic address: yukim@yuhs.ac.
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D007166:Immunosuppressive Agents / Q000633:toxicity*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009173:Mycophenolic Acid / Q000633:toxicity*; D011485:Protein Binding; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D020798:Two-Hybrid System Techniques; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; C000594050:PRMT3 protein, rat; D011484:Protein-Arginine N-Methyltransferases; D009173:Mycophenolic Acid