Nuclear and membrane receptor-mediated signalling pathways modulate polyamine biosynthesis and interconversion.
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 N(1)-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.
Grzelakowska-Sztabert
B
B
Nencki Institute of Experimental Biology, Pasteur 3, 02-093 Warsaw, Poland. b.grzelakowska@nencki.gov.pl
Dudkowska
M
M
Manteuffel-Cymborowska
M
M
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000818:Animals; D005492:Folic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D005493:Folic Acid Antagonists / Q000633:toxicity; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000502:physiology; D006984:Hypertrophy; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051379:Mice; D009955:Ornithine Decarboxylase / Q000235:genetics; D011073:Polyamines / Q000378:metabolism*; D011799:Quinazolines / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology*
D005493:Folic Acid Antagonists; D011073:Polyamines; D011799:Quinazolines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013739:Testosterone; D017228:Hepatocyte Growth Factor; C031662:CB 3717; D005492:Folic Acid; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase