Response of enzymes involved in the metabolism of polyamines to phytohaemagglutinin-induced activation of human lymphocytes

Abstract

The stimulation of lymphocyte ornithine decarboxylase and adenosylmethionine decarboxylase produced by phytohaemagglutinin was accompanied by an equally marked, but delayed, stimulation of spermidine synthase, which is not commonly considered as an inducible enzyme. In contrast with the marked stimulation of these biosynthetic enzymes, less marked changes were observed in the biodegradative enzymes of polyamines in response to phytohaemagglutinin. Diamine oxidase activity was undetectable during all stages of the transformation. The activity of polyamine oxidase remained either constant or was slightly decreased several days after addition of the mitogen. The activity of polyamine acetylase (employing all the natural polyamines as substrates) distinctly increased both in the cytosolic and crude nuclear preparations of the cells during later stages of mitogen activation. Difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, although powerfully inhibiting ornithine decarboxylase, produced a gradual enhancement of adenosylmethionine decarboxylase activity during lymphocyte activation, without influencing the activities of the two propylamine transferases (spermidine synthase and spermine synthase).

Inhibition of spermidine synthase gene expression by transforming growth factor-β1 in hepatoma cells

“…Although spermidine synthase has been regarded as a nonrate-limiting and stable enzyme [2,4], previous reports have also shown the inducible nature of its enzymic activity during cell proliferation in several experimental systems [7][8][9][10]. To our knowledge, the present study is the first to show that the gene expression of spermidine synthase is also highly regulated.…”

“…Spermidine synthase and spermine synthase have been regarded as non-rate-limiting and stable enzymes which are regulated mainly by the availability of the substrate, decarboxylated AdoMet, and by the product, 5h-methylthioadenosine (MTA) [2,4]. However, some previous reports on spermidine synthase have shown it to be inducible during cell proliferation, such as liver regeneration and liver compensatory growth [7], hormone-induced growth of tissues [8,9] and lectininduced lymphocyte activation [10]. Although the human spermidine synthase gene has been cloned [11,12], there have been few reports concerning its expression.…”

Transgenic mice over-expressing the human spermidine synthase gene

“…The best example ofthe latter conditions is the activation of peripheral human lymphocytes in response to an exposure to lectins. Spermidine synthase activity was increased more than 10fold after a phytohaemagglutinin exposure of 48 h (Korpela et al, 1981). The extent of this stimulation was fully comparable with the changes found in the activities of ornithine and adenosylmethionine decarboxylases, and was believed to contribute to the swift accumulation of spermidine during lymphocyte activation (Korpela et al, 1981).…”

“…Spermidine synthase activity was increased more than 10fold after a phytohaemagglutinin exposure of 48 h (Korpela et al, 1981). The extent of this stimulation was fully comparable with the changes found in the activities of ornithine and adenosylmethionine decarboxylases, and was believed to contribute to the swift accumulation of spermidine during lymphocyte activation (Korpela et al, 1981). Our present results with transgenic mice over-expressing spermidine synthase seem to indicate that grossly elevated tissue activity of the latter enzyme had only a marginal effect on tissue spermidine and spermine concentrations, as did the combined over-expression of ornithine decarboxylase and spermidine synthase in the transgenic hybrid mice (Table 2).…”

“…The regulation of spermidine and spermine synthases is believed to occur at the level of the availability of their common substrate, decarboxylated adenosylmethionine (Janne et al, 1978;Pegg, 1986). Although these propylamine transferases are not commonly considered as inducible enzymes, there are reports showing that spermidine synthase activity responds to mitogenic stimuli, such as lectininduced lymphocyte activation (Korpela et al, 1981), hormoneinduced tissue proliferation (Oka et al, 1977;Kapyaho et al, 1980) and compensatory growth of rodent liver (Hannonen et al, 1972).…”