Expression of inosine monophosphate dehydrogenase type I and type II after mycophenolate mofetil treatment: a 2-year follow-up in kidney transplantation.
The objective of the study was to evaluate the effect of mycophenolate mofetil (MMF) on the regulation of inosine monophosphate dehydrogenase (IMPDH) during the first 2 years after renal transplantation. Twelve patients were enrolled, and 10-h time-course evaluations of the effects of MMF were regularly performed during the study. IMPDH activity and gene expression were measured in whole blood and in mononuclear cells, respectively. Type I IMPDH (IMPDH-I) mRNA was increased during the first 3 months following transplantation and reached its maximal level during acute rejection episodes, whereas type II IMPDH mRNA was stable. Furthermore, although no alteration in the predose samples was observed, patients with prolonged MMF treatment exhibited an increase in the induction potency of both IMPDH activity and gene expression. In vitro experiments confirmed that IMPDH-I is inducible, but preferentially in monocytes than in lymphocytes. This finding suggests that the measurement of IMPDH mRNAs may provide reliable information to predict acute rejection.
Sanquer
S
S
Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Biochimie, Paris, France. sylvia.sanquer@gmail.com
Maison
P
P
Tomkiewicz
C
C
Macquin-Mavier
I
I
Legendre
C
C
Barouki
R
R
Lang
P
P
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006084:Graft Rejection / Q000201:enzymology / Q000517:prevention & control*; D006801:Humans; D007168:IMP Dehydrogenase / Q000097:blood* / Q000235:genetics; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016030:Kidney Transplantation; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D015415:Biomarkers; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human; C501687:IMPDH2 protein, human; D009173:Mycophenolic Acid