Covalent modification of rat liver dipeptidyl peptidase IV (CD26) by the nonsteroidal anti-inflammatory drug diclofenac.
Diclofenac is a nonsteroidal anti-inflammatory drug that has been implicated in several cases of severe hepatotoxicity. Our previous study showed that diclofenac metabolites bound covalently and selectively to rat liver plasma membrane proteins with estimated monomeric masses of 110, 140, and 200 kDa. We report here that we have identified the 110 kDa diclofenac-labeled protein in rat liver as dipeptidyl peptidase IV, also known as CD26. In addition, we found that the activity of dipeptidyl peptidase IV in liver plasma membrane fractions was lowered after diclofenac treatment of rats. These results suggest that the hepatotoxicity associated with diclofenac might be due, in part, to the covalent modification of dipeptidyl peptidase IV.
Hargus
S J
SJ
Molecular and Cellular Toxicology Section, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland 20892, USA.
Martin
B M
BM
George
J W
JW
Pohl
L R
LR
D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004008:Diclofenac / Q000378:metabolism / Q000494:pharmacology*; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D018819:Dipeptidyl Peptidase 4