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Effect of methylglyoxal bis(guanylhydrazone) on polyamine metabolism in normal and regenerating rat liver and rat thymus.

ABSTRACT: 1. Injections of sublethal doses of methylglyoxal bis(guanylhydrazone), a potent inhibitor of putrescine-activated S-adenosylmethionine decarboxylase in vitro, resulted after a few days in an immense increase in the activity of S-adenosylmethionine decarboxylase in normal and regenerating rat liver and in rat thymus. The increase in the activity of S-adenosylmethionine decarboxylase was at least partly due to a marked lengthening of the half-life of the enzyme. 2. In regenerating liver and thymus there was also a moderate stimulation of the activity of ornithine decarboxylase (EC 4.1.1.17) and a marked accumulation of tissue putrescine. 3. Injection of methylglyoxal bis(guanylhydrazone) into the rat also markedly decreased the activity of diamine oxidase (EC 1.4.3.6) in thymus. 4. In no cases where doses of methylglyoxal bis(guanylhydrazone) close to the LD(50) dose for the rat were used was it possible to lower tissue spermidine content to any significant extent. 5. Methylglyoxal bis(guanylhydrazone) seemed to act as a competitive inhibitor for the substrate S-adenosylmethionine and as an uncompetitive inhibitor for the activator putrescine in the decarboxylation of S-adenosylmethionine in vitro. 6. In the diamine oxidase reaction, with putrescine as the substrate, methylglyoxal bis(guanylhydrazone) was a non-competitive inhibitor for putrescine.

SUBMITTER: Holtta E

PROVIDER: S-EPMC1166002 | biostudies-other | 1973 Nov

REPOSITORIES: biostudies-other

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Inhibition of spermidine formation in rat liver and kidney by methylglyoxal bis(guanylhydrazone).

Project description:The effect of methylglyoxal bis(guanylhydrazone), a substance known to inhibit putrescine-dependent S-adenosyl-l-methionine decarboxylase, on polyamine metabolism in liver and kidney was investigated. Almost complete inhibition of the incorporation of putrescine into spermidine was obtained up to 8h after administration of 80mg of methylglyoxal bis(guanylhydrazone)/kg body wt. by intraperitoneal injection. However, by 20h after administration of the inhibitor spermidine synthesis was resumed. Considerable accumulation of putrescine occurred during this period (up to 3 times control concentrations in both tissues), but there was only a slight fall in the spermidine content. These results suggest that the putrescine-activated S-adenosyl-l-methionine decarboxylase plays an essential role in spermidine biosynthesis in rat liver and kidney, and the possibility of using methylglyoxal bis(guanylhydrazone) to study the role of polyamine synthesis in growth is discussed.

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Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone.

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Direct Targeting of Macrophages With Methylglyoxal-Bis-Guanylhydrazone Decreases SIV-Associated Cardiovascular Inflammation and Pathology.

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