Studies on the effects of an ornithine decarboxylase inhibitor on lupus nephritis reveal a post-transcriptional modification of the enzyme

H. C. Hsu; T. Thomas; J. R. Seibold; T. J. Thomas

doi:10.1007/BF01972767

Studies on the effects of an ornithine decarboxylase inhibitor on lupus nephritis reveal a post-transcriptional modification of the enzyme

H. C. Hsu, T. Thomas, J. R. Seibold, T. J. Thomas

Robert Wood Johnson Medical School (RWJMS), Medicine, Division of Rheumatology

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Abstract

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.

Original language	English (US)
Pages (from-to)	C204-C206
Journal	Agents and Actions
Volume	39
Issue number	1 Supplement
DOIs	https://doi.org/10.1007/BF01972767
State	Published - Mar 1993

All Science Journal Classification (ASJC) codes

Toxicology
Pharmacology (medical)

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title = "Studies on the effects of an ornithine decarboxylase inhibitor on lupus nephritis reveal a post-transcriptional modification of the enzyme",

abstract = "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.",

author = "Hsu, {H. C.} and T. Thomas and Seibold, {J. R.} and Thomas, {T. J.}",

year = "1993",

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AU - Hsu, H. C.

AU - Thomas, T.

AU - Seibold, J. R.

AU - Thomas, T. J.

PY - 1993/3

Y1 - 1993/3

N2 - 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.

AB - 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.

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Studies on the effects of an ornithine decarboxylase inhibitor on lupus nephritis reveal a post-transcriptional modification of the enzyme

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