Effect of polyamine analogues on hypusine content in JURKAT T-cells.
The availability of synthetic hypusine and deoxyhypusine has made it possible to develop analytical methods which allow for the measurement of these compounds in various tissues. The methods involve dansylation of extracts from the pellet remaining after perchloric acid precipitation of cell or tissue homogenates, followed by high-performance liquid chromatography. To demonstrate the utility of this approach, the impact of four polyamine analogues, N1,N11-diethylnorspermine (DENSPM), N1,N14-diethylhomospermine (DEHSPM), 1,6,12-triazadodecane [(4,5) triamine], and 1,7, 13-triazatridecane [(5,5) triamine], on hypusine levels in a human T-cell line (JURKAT) is evaluated. All four analogues are active in controlling cell growth and compete well with spermidine for the polyamine transport apparatus. After 144 h of exposure to JURKAT cells, DENSPM reduces putrescine to below detectable limits and spermidine to 10% of the level in control cells. The other three analogues diminish both putrescine and spermidine to below detectable limits. The effectiveness with which the compounds lower spermine levels is DENSPM > DEHSPM > (4,5) triamine > (5,5) triamine. The analogues decrease the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase in a similar fashion. Of the four polyamines, DENSPM and DEHSPM are potent at lowering intracellular hypusine levels after 144 h: 59 +/- 9% and 73 +/- 12% of control levels, respectively. The other two analogues have marginal effects.
Bergeron
R J
RJ
Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610-0485, USA.
Weimar
W R
WR
Müller
R
R
Zimmerman
C O
CO
McCosar
B H
BH
Yao
H
H
Smith
R E
RE
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003619:Dansyl Compounds / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D007939:Leukemia L1210 / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry; D065108:Ornithine Decarboxylase Inhibitors; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003619:Dansyl Compounds; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; C058306:N(1),N(14)-bis(ethyl)homospermine; C059685:N(1),N(11)-diethylnorspermine; D013096:Spermine; C100028:hypusine; C034924:deoxyhypusine; D012437:Adenosylmethionine Decarboxylase; D008239:Lysine; D013095:Spermidine