Methylglyoxal-bis(cyclopentylamidinohydrazone) (MGBCP) has been synthesized as a multienzyme inhibitor for the polyamine-synthesizing pathway. This drug inhibited S-adenosylmethionine decarboxylase (EC 4.1.1.50), spermine synthase and spermidine synthase activities, competitively with S-adenosylmethionine, spermidine, and putrescine, respectively. MGBCP inhibited the growth of human leukemia Mo...

Kidney ischemia and reperfusion injury (IRI) is associated with a high mortality rate, which is attributed to tubular oxidative and nitrative stresses; however, an effective approach to limit IRI remains elusive. Spermidine, a naturally occurring polyamine, protects yeast cells against aging through the inhibition of oxidative stress and necrosis. In the present study, spermidine supplementatio...

Trypanosomatid parasites containing a metabolically unstable ornithine decarboxylase (ODC) are naturally resistant to high levels of alpha-difluoromethylornithine (DFMO) because this ODC inhibitor, though causing a drastic reduction of intracellular putrescine, elicits only a moderate decrease of the spermidine endogenous pool. In this study we have used a combination of DFMO with cyclohexylami...

Spergualin (SG) and 15-deoxyspergualin (DSG) were more slowly incorporated into L5178Y cells than spermidine. SG and DSG inhibited carrier-mediated transport of [3H]spermidine competitively with inhibition constants of 0.67 mM and 0.45 mM, respectively. Addition of calf serum stimulated uptake of [3H]spermidine into the cells in a serum concentration-dependent manner. The effect was not observe...

Evidence obtained from experiments with rats and mice is presented suggesting that the naturally occurring amino acids putreanine and N8-(2-carboxyethyl)spermidine, and most probably also related compounds deriving from the polyamines spermidine and spermine by oxidative metabolism, are formed within two anatomical compartments. In the first step polyamines are converted into aldehydes by serum...

Polyamine concentrations were evaluated in normal human prostatic tissue as well as hyperplastic prostate. Normal tissues had high concentrations of putrescine and spermine with intermediate spermidine concentrations, whereas there was a dramatic increase in the spermine concentration in patients with hypertrophy of the prostate. Although not highly significant, spermidine concentrations were e...

Spermidine is a natural polyamine involved in many important cellular functions, whose supplementation in food or water increases life span and stress resistance in several model organisms. In this work, we expand spermidine's range of age-related beneficial effects by demonstrating that it is also able to improve locomotor performance in aged flies. Spermidine's mechanism of action on aging ha...

The administration of [14C]putrescine or [14C]spermidine (i.v., 100 muCi) to normal volunteers or patients with advanced cancer resulted in alpha-phase half-lives of 40 and 30 sec and beta-phase half-lives of 30 and 60 min, respectively. No significant differences were found between the plasma decay curves of normals and those of cancer patients. Urinary excretion was similar with both groups e...

Lysosomal cystine transport is a carrier-dependent process that, in isolated lysosomes, is stimulated by proton gradients, membrane potential, and millimolar concentrations of divalent cations. The importance of these regulatory factors in vivo is not well established. Polyamines were found to stimulate cystine transport in Percoll gradient purified rat liver lysosomes with spermidine greater t...

Putrescine and spermidine uptake into carrot (Daucus carota L.) cells in culture was studied. The time course of uptake showed that the two polyamines were very quickly transported into the cells, reaching a maximum absorption within 1 minute. Increasing external polyamine concentrations up to 100 millimolar showed the existence of a biphasic system with different affinities at low and high pol...