Polyamine homeostasis in arginase knockout mice.
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-N(1)-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 arginase-derived ornithine may not directly contribute to polyamine homeostasis in mice. Alternate sources such as diet may provide sufficient polyamines for maintenance in mammalian tissues.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1732, USA.
Joshua L
JL
Deignan
Justin C
JC
Livesay
Lisa M
LM
Shantz
Anthony E
AE
Pegg
William E
WE
O'Brien
Ramaswamy K
RK
Iyer
Stephen D
SD
Cederbaum
Wayne W
WW
Grody
D000123:Acetyltransferases / Q000235:genetics; D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics; D000818:Animals; D001119:Arginase / Q000235:genetics*; D015317:Biogenic Polyamines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D015870:Gene Expression; D006706:Homeostasis / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009955:Ornithine Decarboxylase / Q000378:metabolism; D009953:Ornithine-Oxo-Acid Transaminase / Q000235:genetics; D011506:Proteins / Q000235:genetics; D011700:Putrescine / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D006631:Amine Oxidase (Copper-Containing); D001119:Arginase; D015317:Biogenic Polyamines; D009955:Ornithine Decarboxylase; D009953:Ornithine-Oxo-Acid Transaminase; D011506:Proteins; D011700:Putrescine; D012333:RNA, Messenger; D013095:Spermidine; D013096:Spermine; D000099228:Diamine N-Acetyltransferase; C031017:ornithine decarboxylase antizyme; C481673:Arg2 protein, mouse