PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Biogenic Polyamines”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1989

Polyamines induce precocious development in rats. Possible interaction with growth factors.

The study reports the effects of daily subcutaneous injections of the biogenic polyamines putrescine, spermidine and spermine (10 mg/kg each) given for a short postnatal period, on growth and development of rats. Polyamine treatment, while only slightly enhancing normal body weight gain, prevented the weight loss caused by surgical injury of 5-day-old animals. The treatment resulted in earlier eyelid and ear opening and in earlier maturation of righting and gripping responses. Increased number of neurons in the superior cervical ganglion that is caused by polyamine treatment, could not be prevented by castration of newborn rats, thus excluding the testes as a site through which polyamines may exert their action. An apparent increase in immunohistochemically detectable nerve growth factor was evident in iris and submaxillary salivary gland of polyamine-treated animals, but no change in epidermal growth factor immunohistochemistry was detected in the salivary gland. We conclude: (1) treatment of newborn rats with polyamines can accelerate somatic and neurobehavioral development; (2) further studies are required in order to verify and quantitate the effects of polyamines on growth factors, and (3) the results imply that exogenous polyamines may exert their growth-promoting effects on a number of cell types when these cells experience periods of polyamine dependence.

Animals↗
PubMed1978

Polyamine interaction with pregnancy serum in suppression of lymphocyte transformation.

Biogenic polyamines interacting with pregnancy serum elicit potent suppression of lymphocyte transformation in vitro. Within the assay limits, activity was first shown after about 15 weeks' gestation and reached its highest level at about 28 weeks. This level was maintained until term. It is thought that specific humoral amine oxidases were the cause. Fetal-cord serum and non-pregnancy serum were inactive. This system may have an immunoregulatory function in pregnancy.

Animals↗
PubMed1989

Excretion of acetylated and free polyamines by polyamine depleted Chinese hamster ovary cells.

1. Cultured Chinese hamster ovary cells (CHO) and their ornithine decarboxylase deficient mutant cells (C55.7) were found to excrete small amounts of N8-acetylspermidine and free polyamines, putrescine and spermidine into the culture medium. 2. The concentration of N8-acetylspermidine in the control cells was 2-3% of that of spermidine. In the medium, however, the amount of N8-acetylspermidine was about 2-fold that of spermidine and 2- to 3-fold higher than the intracellular amount. N1-acetylspermidine or acetylated spermine were never detected in the cells or in the media. 3. Confluent CHO cells treated with 2 mM difluoromethylornithine stopped the excretion when the intracellular spermidine concentration had decreased to 20% of control while there was no decrease in spermine concentration. At low cell density, neither polyamine depleted CHO cells nor the C55.7 cells excreted any polyamines into the culture media.

Animals↗
PubMed1992

Synergistic antiproliferative activity of human fibroblast interferon in combination with alpha-difluoromethylornithine against human gastric cancer cells in vitro.

The author has studied the effects of alpha-difluoromethylornithine (alpha DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase; human fibroblast interferon (IFN beta); and their combination on human gastric cancer cell growth in vitro. alpha DFMO (from 0.1 to 4 mmol/l) inhibited cell growth in a dose-dependent manner. Both alpha DFMO (0.1 mmol/l) and higher doses of IFN beta (100 and 1000 IU/ml) caused only limited inhibition of cell growth. When alpha DFMO (0.1 mmol/l) was administered in combination with IFN beta (100 and 1000 IU/ml), synergistic antiproliferative activity was observed 7 days after continuous exposure. Although the mechanisms by which this effect occurs are unclear, it appears to be associated with direct inhibition of tumor cell proliferation, possibly by modulation of polyamine metabolism.

Adenocarcinoma↗
PubMed1991

Differential response of rat brain polyamines to convulsant agents.

The polyamines putrescine (PUT), spermidine (SD) and spermine (SM) have been studied in rat brain after treatment with several convulsant agents. Kainic acid (10 mg/kg), picrotoxinin (1.5 mg/kg), pentylenetetrazol (60 mg/kg) and lindane (gamma-hexachlorocyclohexane) (60 mg/kg) were given to male Wistar rats. Twenty-four hours later, the animals were sacrificed and their brains removed. Cortical polyamines were analyzed by HPLC with fluorimetric detection of their respective dansyl derivatives, using 1,6-diaminohexane as internal standard for the measurements. Polyamine levels are not affected by short periods of time (30 min) of brain exposure to room temperature before freezing the samples, as compared to a quick procedure (less than 40 s from animal death). Kainic acid induced a 14-fold increase of cortical PUT with respect to control values, leaving unchanged the other polyamines. Lindane also increased cortical PUT (4-fold) without affecting SM or SD. Neither picrotoxinin, nor pentylenetetrazol groups were different from controls for any of the polyamines assayed. The results are discussed in relation to the possible mechanism of action of these convulsant agents and the role of the polyamines in cell injury.

Animals↗
PubMed1992

Polyamine metabolism in epileptic cortex.

Polyamine (tissue) concentrations have been studied in hippocampus and temporal neocortex from patients with temporal lobe epilepsy. Depth electrode recordings demonstrated hippocampal origin of the seizures, the temporal neocortex being involved during the discharge propagation. Neuropathological examination of excised tissues showed glial proliferation or glioma in Ammon's horn (CA), whereas the temporal neocortex did not exhibit any histological abnormality. Polyamine (putrescine or PUT, spermidine or SPD, spermine or SPM) concentrations were determined on surgical samples from the hippocampus and various areas of temporal neocortex. Human post-mortem tissue from temporal lobe regions was used for controls. In post-mortem controls and temporal neocortex specimens from epileptic patients, polyamine levels were similar (in nmol/g wet weight: PUT = 40-100; SPD = 200-350; SPM = 100-200). In CA, polyamine levels exhibited striking changes: SPD content was significantly increased (350-700 nmol/g) while SPM was lowered (50-100). PUT was only increased in CA invaded by the tumoral process (100-180). Accordingly, a very high SPD/SPM molar ratio in the abnormal CA region was observed, indicating an acceleration of polyamine neosynthesis which is usually related to ornithine decarboxylase induction. Metabolic changes in polyamines appear to be selective of human epileptic hippocampus. A relationship between glial proliferation (gliosis or neoplasia), epileptic firing and polyamines is discussed.

Adult↗
PubMed1990

Polyamine metabolism.

Currently, two major pathways are distinguished along which the polyamines are metabolized: the interconversion pathway and the so-called terminal polyamine catabolism. In vertebrates, the interconversion pathway is a cyclic process which controls polyamine turnover. In conjunction with polyamine transport, it regulates intracellular polyamine homeostasis. In vertebrates, putrescine, the precursor of spermidine and spermine, is exclusively formed by decarboxylation of ornithine--as far as de novo synthesis is concerned. Spermidine and spermine synthase form spermidine from putrescine, and spermine from spermidine, by transfer of aminopropyl residues from decarboxylated S-adenosylmethionine. In the catabolic branch of the interconversion cycle, spermine is degraded to spermidine, and spermidine to putrescine. The first step in this sequence is acetylation in the N1 position. This is followed by oxidative splitting of the acetylated polyamines, whereby the aminopropyl residues which originated from decarboxylated S-adenosylmethionine are removed. The enzyme catalyzing this step is an FAD-dependent oxidase (polyamine oxidase). Ornithine decarboxylase, S-adenosylmethionine decarboxylase, and acetyl CoA:polyamine N1-acetyltransferase are highly regulated, inducible enzymes with a high turnover rate. Depending on the physiological situation, each of these enzymes may become rate limiting. Terminal polyamine catabolism is catalyzed by Cu2(+)-dependent amine oxidases, of which only diamine oxidase has been well defined. By oxidative deamination of a primary amino group, each intermediate of the interconversion cycle can be transformed into an aldehyde, which is further oxidized to an amino acid or a gamma-lactam. The products of the terminal catabolism as well as the acetylated polyamines are urinary excretory products. In addition to intracellularly synthesized polyamines, polyamines from various tissues and from exogenous sources (such as the gastrointestinal tract) may be utilized by those tissues which have a high demand. Polyamines play a paramount role in growth processes. In order to control growth (for example of tumors), it is necessary to block all major polyamine sources. If only one source is blocked, the remaining sources are usually capable of furnishing sufficient polyamines to support growth processes.

Acetylation↗
PubMed1991

Spider toxins affecting glutamate receptors: polyamines in therapeutic neurochemistry.

Polyamine amide toxins obtained from venous of spiders and wasps interact selectively with ionotropic glutamate receptors (GLU-R) of vertebrate central nervous systems. The sites and modes of action of these polyamine amide toxins are reviewed with particular reference to their structure-activity relationships. Qualitatively, their effects on GLU-R are identical to those exerted by polyamines such as spermine, but the polyamine amides are more potent. These compounds (a) potentiate and (b) antagonize GLU-R, the latter arising through open channel block. For the N-methyl-D-aspartate receptor this non-competitive antagonism probably arises through binding of toxin to the Mg2+ site(s) located in the channel gated by this receptor. Similarities and differences between GLU-R in vertebrates and in invertebrates with respect to their interactions with polyamines and polyamine amide toxins are discussed. In both groups the low specificity of these compounds is illustrated by their antagonism at nicotinic acetylcholine receptors in addition to GLU-R. Electrophysiological studies, including those employing Xenopus oocytes, are reviewed and future prospects for the use of polyamine amides in therapy are discussed.

Animals↗
PubMed1992

alpha-Difluoromethylornithine alters calcium signaling in platelet-derived growth factor-stimulated A172 brain tumor cells in culture.

alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of the polyamine biosynthetic enzyme ornithine decarboxylase, inhibits the growth of brain tumor cell lines and is undergoing clinical trials as a treatment for brain tumors. Platelet-derived growth factor (PDGF) is thought to regulate the growth and development of precursors of both normal and neoplastic astrocytic cells; calcium signaling is thought to play a role in the transduction of PDGF signals. Using laser fluorescence image cytometry, flow cytometry, and spectrofluorometry, we studied the effect of DFMO on the calcium signals induced by PDGF in A172 human glioblastoma cells. Four days of treatment with 5 mM DFMO substantially shortened PDGF-induced calcium signals. The effect was reversed more than 10 h but less than 24 h after putrescine treatment, even though polyamines were repleted 4 h after putrescine and spermidine were added. DFMO did not substantially affect intracellular calcium release or the timing of the opening and closing of plasma membrane calcium channels. These findings support the notion that calcium signaling may be a target for inhibitors of polyamine metabolism.

Biogenic Polyamines↗
PubMedDate not supplied

Behavioral and neurochemical sequelae in young rats of antenal hypoxia.

To test the hypothesis that perinatal hypoxia may have postnatal consequences via à vis learning memory, and neurochemical sequelae, we exposed pregnant Sprague-Dawley rats to 10.5% O2 for 4 h per day (0800-1200 h) or continuously from gestional day E15 to E20. On E20 we quantified ornithine decarboxylase activity and polyamine concentrations in fetal brain. We also conducted behavioral tests from postnatal day P3 to P110. Relatively mild antenatal hypoxia resulted in altered learning, memory, and delayed maturation of early developmental sensorimotor function. These behavioral changes disappeared at various postnatal ages, depending on the function. Perinatal hypoxia also altered the pharmacological response to dopaminergic drugs. In addition, antenatal hypoxia feminized a male nonreproductive sexual behavior, that of saccharin preference. Acute hypoxia also resulted in an increase in the enzyme ornithine decarboxylase and polyamines, which may affect brain development.

Animals↗
PubMed1992

Inhibition of deoxyribonucleic acid synthesis by difluoromethylornithine. Role of polyamine metabolism in monocrotaline-induced pulmonary hypertension.

Previously, we have shown that the protection provided by 2-difluoromethylornithine (DFMO) against the development of monocrotaline (MCT)-induced pulmonary hypertension (PH) is associated with inhibition of polyamine biosynthesis in the lungs of MCT-treated rats. Although these studies suggest that prevention of the development of MCT-induced PH is polyamine dependent, no one has demonstrated which cellular events of MCT-induced PH are polyamine dependent. In the present study, using DFMO we tested the hypothesis that inhibition of polyamine biosynthesis may protect against MCT-induced PH by limiting increases in DNA synthesis. We injected rats with MCT (60 mg/kg) or 0.9% NaCl and measured DNA synthesis 7 days after MCT by determining [3H]thymidine incorporation into whole lung DNA. We found that 7 days after MCT treatment DNA synthesis was increased compared to the control (0.9% NaCl). However, DFMO treatment (2% in drinking water) reduced the increase in DNA synthesis following MCT. To confirm that DFMO was acting as a specific inhibitor of polyamine biosynthesis in MCT-induced PH, we administered DFMO concurrently with exogenous ornithine (ORN) (2% in drinking water), the substrate for polyamine biosynthesis, to reverse the protection afforded by DFMO against MCT-induced PH. Twenty-one days after MCT injection we examined right ventricular hypertrophy (RVH), mean pulmonary arterial pressure (MPAP), lung wet weight, and lung polyamine levels. While animals given DFMO (MCT + DFMO) did not increase RVH, MPAP, lung wet weight, or lung polyamine levels, animals given ORN (MCT + DFMO + ORN) did develop increases paralleling those found in animals treated with MCT alone. Our results suggest that suppression of polyamine biosynthesis by DFMO may protect against the development of MCT-induced PH in part by preventing increases in DNA synthesis. This suppression of DNA synthesis may limit the proliferation of key lung cells involved in the inappropriate vascular remodelling associated with MCT-induced PH. These results are consistent with our working hypothesis that elevated lung polyamine levels are essential for the development of MCT-induced PH.

Animals↗