Polyamine homeostasis in arginase knockout mice

Joshua L. Deignan, Justin C. Livesay, Lisa M. Shantz, Anthony E. Pegg, William E. O'Brien, Ramaswamy K. Iyer, Stephen D. Cederbaum, Wayne W. Grody

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The role of ornithine decarboxylase (ODC) in polyamine metabolism has long been established, but the exact source of ornithine has always been unclear. The arginase enzymes are capable of producing ornithine for the production of polyamines and may hold important regulatory functions in the maintenance of this pathway. Utilizing our unique set of arginase single and double knockout mice, we analyzed polyamine levels in the livers, brains, kidneys, and small intestines of the mice at 2 wk of age, the latest timepoint at which all of them are still alive, to determine whether tissue polyamine levels were altered in response to a disruption of arginase I (AI) and II (AII) enzymatic activity. Whereas putrescine was minimally increased in the liver and kidneys from the AII knockout mice, spermidine and spermine were maintained. ODC activity was not greatly altered in the knockout animals and did not correlate with the fluctuations in putrescine. mRNA levels of ornithine aminotransferase (OAT), antizyme 1 (AZ1), and spermidine/spermine-N1-acetyltransferase (SSAT) were also measured and only minor alterations were seen, most notably an increase in OAT expression seen in the liver of AI knockout and double knockout mice. It appears that putrescine catabolism may be affected in the liver when AI is disrupted and ornithine levels are highly reduced. These results suggest that endogenous arginas-ederived ornithine may not directly contribute to polyamine homeostasis in mice. Alternate sources such as diet may provide sufficient polyamines for maintenance in mammalian tissues.

Original languageEnglish (US)
Pages (from-to)C1296-C1301
JournalAmerican Journal of Physiology - Cell Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 1 2007

Fingerprint

Arginase
Polyamines
Knockout Mice
Homeostasis
Ornithine
Putrescine
Ornithine-Oxo-Acid Transaminase
Ornithine Decarboxylase
Spermine
Liver
Maintenance
Kidney
Spermidine
Small Intestine
Diet
Messenger RNA
Brain
Enzymes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

Deignan, J. L., Livesay, J. C., Shantz, L. M., Pegg, A. E., O'Brien, W. E., Iyer, R. K., ... Grody, W. W. (2007). Polyamine homeostasis in arginase knockout mice. American Journal of Physiology - Cell Physiology, 293(4), C1296-C1301. https://doi.org/10.1152/ajpcell.00393.2006
Deignan, Joshua L. ; Livesay, Justin C. ; Shantz, Lisa M. ; Pegg, Anthony E. ; O'Brien, William E. ; Iyer, Ramaswamy K. ; Cederbaum, Stephen D. ; Grody, Wayne W. / Polyamine homeostasis in arginase knockout mice. In: American Journal of Physiology - Cell Physiology. 2007 ; Vol. 293, No. 4. pp. C1296-C1301.
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Deignan, JL, Livesay, JC, Shantz, LM, Pegg, AE, O'Brien, WE, Iyer, RK, Cederbaum, SD & Grody, WW 2007, 'Polyamine homeostasis in arginase knockout mice', American Journal of Physiology - Cell Physiology, vol. 293, no. 4, pp. C1296-C1301. https://doi.org/10.1152/ajpcell.00393.2006

Polyamine homeostasis in arginase knockout mice. / Deignan, Joshua L.; Livesay, Justin C.; Shantz, Lisa M.; Pegg, Anthony E.; O'Brien, William E.; Iyer, Ramaswamy K.; Cederbaum, Stephen D.; Grody, Wayne W.

In: American Journal of Physiology - Cell Physiology, Vol. 293, No. 4, 01.10.2007, p. C1296-C1301.

Research output: Contribution to journalArticle

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