COMBINED REGULATION OF ORNITHINE AND S-ADENOSYLMETHIONINE DECARBOXYLASES BY SPERMINE AND THE SPERMINE ANALOG N1N12-BIS(ETHYL)SPERMINE

被引:61
作者
PORTER, CW
PEGG, AE
GANIS, B
MADHABALA, R
BERGERON, RJ
机构
[1] PENN STATE UNIV, MILTON S HERSHEY MED CTR, COLL MED, DEPT PHYSIOL, HERSHEY, PA 17033 USA
[2] PENN STATE UNIV, MILTON S HERSHEY MED CTR, COLL MED, CANC RES CTR, HERSHEY, PA 17033 USA
[3] UNIV FLORIDA, J HILLIS MILLER HLTH CTR, DEPT MED CHEM, GAINESVILLE, FL 32610 USA
关键词
D O I
10.1042/bj2680207
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In the present study, the spermine (SPM) analogue N1N12-bis(ethyl)spermine (BESPM) is compared with SPM in its ability to regulate ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (AdoMetDC) activities in intact L1210 cells and in the mechanisms(s) by which this is accomplished. Unlike the comparable spermidine (SPD) analogue N1N8-bis(ethyl)spermidine, which regulates only ODC, BESPM suppresses both ODC and AdoMetDC activities. With 1 μM-SPM or -BESPM, near-maximal suppression of enzyme activity (i.e. < 70%) was achieved after 2 h for ODC and 12 h for AdoMetDC. After such treatment, ODC activity fully recovered within 2-4 h, and that of AdoMetDC within 12 h, when cells were reseeded into drug-free media. It was deduced that an intracellular accumulation of BESPM or SPM equivalent to only ~ 200-450 pmol/106 cells was sufficient to fully invoke ODC regulatory mechanisms. Decreases in both enzyme activities after BESPM or SPM treatment were closely paralleled by concomitant decreases in the amount of enzyme protein. Since cellular ODC or AdoMetDC mRNA was not similarly decreased by either BESPM or SPM treatment, it was concluded that translational and/or post-translational mechanisms were probably responsible for enzyme regulation. In support of the former of these possibilities, it was demonstrated that both BESPM and SPM preferentially inhibited the translation in vitro of ODC and AdoMetDc relative to albumin in a reticulocyte-lysate system. On the basis of the consistent similarities between BESPM and SPM in all parameters studied, it is concluded that the analogue most likely acts by mechanisms identical with those by which SPM acts in suppressing polyamine biosynthesis.
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页码:207 / 212
页数:6
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