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The modulation of the induction of ornithine decarboxylase by spermine, spermidine and diamines
Author(s) -
Heller John S.,
Chen Kuang Yu,
Kyriakidis Dimitri A.,
Fong Wang F.,
Canellakis E. S.
Publication year - 1978
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1040960211
Subject(s) - putrescine , ornithine decarboxylase , spermidine , spermine , ornithine decarboxylase antizyme , polyamine , intracellular , biochemistry , extracellular , biology , chemistry , microbiology and biotechnology , enzyme
Extremely low concentrations of putrescine, spermidine and spermine added to the extracellular medium of cultures of mammalian cells inhibit the induction of ornithine decarboxylase activity despite 100‐ to 1,000‐fold greater intracellular polyamine concentrations. The diamines, 1,2‐diaminoethane, 1,3‐diaminopropane, 1,5‐diaminopentane, 1,7‐diaminoheptane, 1,10‐diaminodecane, 1,12‐diaminododecane also inhibit ornithine decarboxylase at all concentrations tested (greater than 10 −6 M). In contrast, 10 −6 M to 10 −3 M 1,8‐diaminooctane, the alkyl analog of spermidine, enhances ornithine decarboxylase activity. The concentraton of putrescine required to inhibit the activity of ornithine decarboxylase by 50% is a characteristic of each cell line; however, it varies by as much as 1,000‐fold among the five cell lines we have tested (L1210 leukemic, H35 hepatoma, N18 neuroblastoma, W256 carcinosarcoma and 3T3 fibroblasts). The antizyme to ornithine decarboxylase can be induced in all these cells by high (di)(poly)amine concentrations. Based on these and other experiments we suggest a working hypothesis: that the polyamines regulate ornithine decarboxylase activity through two different sites that may be interrelated; a sensitive membrane‐mediated site that responds to minute fluctuations of extracellular polyamine levels and a coarse site which may be intracellular or membrane associated that responds to larger fluctuations of intracellular polyamine levels. The consequences of such a control mechanism operating within the whole organism are discussed.