PRMT3: New Binding Molecule to RhoGDI-α During Mycophenolic Acid–induced β-cell Death

• Published in: Transplantation proceedings Vol. 46; no. 4; pp. 1229 - 1232
• Main Authors: Huh, K.H, Cho, Y, Kim, B.S, Joo, D.J, Kim, M.S, Kim, Y.S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2014
• Subjects: Animals; Apoptosis - drug effects; Cell Line, Tumor; Gene Expression Regulation; Immunosuppressive Agents - toxicity; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - enzymology; Insulin-Secreting Cells - pathology; Mycophenolic Acid - toxicity; Protein Binding; Protein-Arginine N-Methyltransferases - genetics; Protein-Arginine N-Methyltransferases - metabolism; Rats; rho Guanine Nucleotide Dissociation Inhibitor alpha - genetics; rho Guanine Nucleotide Dissociation Inhibitor alpha - metabolism; Surgery; Time Factors; Two-Hybrid System Techniques
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2013.12.016

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.