Studies on the effects of an ornithine decarboxylase inhibitor on lupus nephritis reveal a post-transcriptional modification of the enzyme.
Upregulation of ornithine decarboxylase (ODC) activity and polyamine levels is found in the kidney of MRL-lpr/lpr (lpr) mouse, an animal model of lupus. To understand the molecular genetics of ODC regulation in lpr mouse, we analyzed ODC mRNA and activity in the kidney of lpr and normal BALB/c and MRL(-)+/+ mice. Although ODC activity was significantly higher in lpr kidney, its mRNA level was lower compared to normal strains, as measured by Northern blot hybridization. Treatment of lpr mouse with difluoromethylornithine (DFMO) reduced ODC activity in lpr kidney to the level of normal strains. In contrast, ODC mRNA level increased 12-fold by DFMO treatment. These results suggest that post-transcriptional modification of ODC in lpr genetic background might be responsible for increased ODC activity and polyamines. The beneficial effect of DFMO on murine lupus suggests a pathogenic role for altered ODC regulation in lpr mouse.
Hsu
H C
HC
Program in Clinical Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903.
Thomas
T
T
Seibold
J R
JR
Thomas
T J
TJ
D000818:Animals; D015152:Blotting, Northern; D000518:Eflornithine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008181:Lupus Nephritis / Q000188:drug therapy / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009693:Nucleic Acid Hybridization; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D012333:RNA, Messenger; D009955:Ornithine Decarboxylase; D000518:Eflornithine