Two mechanisms of spermidine/spermine N1-acetyltransferase-induction.
The changes in activity of spermidine/spermine N1-acetyltransferase (SAT), a rate-limiting enzyme in polyamine degradation, were investigated to understand the mechanism of the induction of this enzyme in bovine lymphocytes. The activity of SAT was induced by stimulation with phytohemagglutinin (PHA), calcium ionophore A23187, sodium n-butyrate, or methylglyoxal bis(guanylhydrazone) (MGBG). When the cells were treated with a combination of PHA with either MGBG or butyrate, the increase in SAT was synergistic. However, the treatment of cells with both PHA and A23187 did not cause more induction of the enzyme activity than the stimulatory effects of each agent alone. The elevation in SAT caused by PHA or A23187 was inhibited by the simultaneous addition of 25 microM H-7, a protein kinase C inhibitor; the induction of the enzyme activity by MGBG or butyrate was slightly enhanced in the presence of H-7. In cells treated with a high concentration of O-tetradecanoylphorbol 13-acetate, which results in the breakdown of protein kinase C, PHA and A23187 did not give the maximum response, and MGBG slightly enhanced the enzyme activity. Dibutyryl cyclic AMP inhibited PHA-induced enzyme activity, but it stimulated MGBG- or butyrate-induced activity. Exposure to PHA or A23187 but not to MGBG or butyrate significantly increased the ornithine decarboxylase activity and DNA synthesis. These results showed that there were two different mechanisms of SAT induction. One is dependent on protein kinase C. The other one is independent of protein kinase C and is enhanced by cyclic AMP.
Matsui-Yuasa
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I
Department of Biochemistry, Osaka City University Medical School, Japan.
Otani
S
S
Yukioka
K
K
Goto
H
H
Morisawa
S
S
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000123:Acetyltransferases / Q000096:biosynthesis*; D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002772:Cholera Toxin / Q000494:pharmacology; D004357:Drug Synergism; D004790:Enzyme Induction; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008935:Mitoguazone / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D000099228:Diamine N-Acetyltransferase
D015056:1-Methyl-3-isobutylxanthine; D000123:Acetyltransferases; D002087:Butyrates; D020148:Butyric Acid; D000001:Calcimycin; D002772:Cholera Toxin; D008935:Mitoguazone; D010835:Phytohemagglutinins; D000099228:Diamine N-Acetyltransferase