Polyamines play an important role in cell growth and differentiation, while their overproduction has potentially oncogenic consequences. Polyamine homoeostasis, a critical determinant of cell fate, is precisely tuned at the level of biosynthesis, degradation and transport. The enzymes ODC (ornithine decarboxylase), AdoMetDC (S-adenosylmethionine decarboxylase) and SSAT (spermidine/spermine N1-acetyltransferase) are critical for polyamine pool maintenance. Our experiments were designed to examine the expression of these enzymes in testosterone-induced hypertrophic and antifolate-induced hyperplastic mouse kidney, characterized by activation of AR (androgen receptor) and HGF (hepatocyte growth factor) membrane receptor c-Met respectively. The expression of these key enzymes was up-regulated by antifolate CB 3717 injury-evoked activation of HGF/c-Met signalling. In contrast, activation of the testosterone/AR pathway remarkably induced a selective increase in ODC expression without affecting other enzymes. Studies in catecholamine-depleted kidneys point to a synergistic interaction between the signalling pathways activated via cell membrane catecholamine receptors and AR, as well as c-Met. We found that this cross-talk modulated the expression of ODC and AdoMetDC, enzymes limiting polyamine biosynthesis, but not SSAT. This is in contrast with the antagonistic cross-talk between AR- and c-Met-mediated signalling which negatively regulated the expression of ODC, but affected neither AdoMetDC nor SSAT.
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April 2007
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Conference Article|
March 20 2007
Nuclear and membrane receptor-mediated signalling pathways modulate polyamine biosynthesis and interconversion
B. Grzelakowska-Sztabert;
B. Grzelakowska-Sztabert
1
1Nencki Institute of Experimental Biology, Pasteur 3, 02-093 Warsaw, Poland
1To whom correspondence should be addressed (email b.grzelakowska@nencki.gov.pl).
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M. Dudkowska;
M. Dudkowska
1Nencki Institute of Experimental Biology, Pasteur 3, 02-093 Warsaw, Poland
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M. Manteuffel-Cymborowska
M. Manteuffel-Cymborowska
1Nencki Institute of Experimental Biology, Pasteur 3, 02-093 Warsaw, Poland
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Publisher: Portland Press Ltd
Received:
September 29 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2007 The Biochemical Society
2007
Biochem Soc Trans (2007) 35 (2): 386–390.
Article history
Received:
September 29 2006
Citation
B. Grzelakowska-Sztabert, M. Dudkowska, M. Manteuffel-Cymborowska; Nuclear and membrane receptor-mediated signalling pathways modulate polyamine biosynthesis and interconversion. Biochem Soc Trans 1 April 2007; 35 (2): 386–390. doi: https://doi.org/10.1042/BST0350386
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