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

 K.H. Huh  ;  Y. Cho  ;  B.S. Kim  ;  D.J. Joo  ;  M.S. Kim  ;  Y.S. Kim 
 TRANSPLANTATION PROCEEDINGS, Vol.46(4) : 1229-1232, 2014 
Journal Title
Issue Date
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 ; Time Factors ; Two-Hybrid System Techniques ; rho Guanine Nucleotide Dissociation Inhibitor alpha/genetics ; rho Guanine Nucleotide Dissociation Inhibitor alpha/metabolism*
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.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Cho, Yu Ri(조유리)
Joo, Dong Jin(주동진) ORCID logo https://orcid.org/0000-0001-8405-1531
Huh, Kyu Ha(허규하) ORCID logo https://orcid.org/0000-0003-1364-6989
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