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Results for “Biogenic Polyamines”

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At least 73 records · Page 4Linked to original sources

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↗

Silica pattern formation in diatoms: species-specific polyamine biosynthesis.

Diatoms are eukaryotic, unicellular algae that are well known for the intricate architecture of their silica-based cell walls. Species identification is mainly based on variations of their hierarchically organized silica structures. Particularly striking silica frameworks are found among diatoms that belong to the genus Coscinodiscus. Recent work indicates an important role for long-chain polyamines in guiding silica precipitation as well as in silica-pattern formation. Here we demonstrate that polyamines, even if isolated from closely related diatom species, exhibit substantial structural differences. Structural variations include the overall chain length, the degree of methylation, positions of secondary amino functionalities, and, unexpectedly, site-specific incorporation of a quaternary ammonium functionality. These findings support a specific role for polyamines in creating silica nanostructures.

Biogenic Polyamines↗

Polyamines modulate the function of transfected glutamate receptor mGluR1a.

Metabotropic glutamate receptor mGluR1a was expressed in human embryonic kidney 293 cells. 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) stimulated dose-dependently, phosphoinositide (PI) hydrolysis in transfected, but not in non-transfected cells. The polyamine spermine did not affect PI hydrolysis in the absence of 1S,3R-ACPD even at a concentration of 1 mM, but it potentiated the stimulatory action of 1S,3R-ACPD at 10 microM. The modulatory action of spermine was mimicked by spermidine but not by the short polyamine putrescine.

Biogenic Polyamines↗

[The relations between polyamine types and forms and polyamine oxidase activities in barley seedlings under salt stress].

The three polyamines (Put, Spd and Spm) and their different forms (free, perchioric acid soluble and insoluble conjugated) together with polyamine oxidase (PAO) activities were measured in barley (Hordeum vulgare L. KP7) seedlings under salt stress. The results showed that the free polyamines were dominant forms among three polyamines, account about 2/3 total polyamines. All three polyamines decreased in roots and leaves after 8 d under NaCl 200 mmol/L stress. The free polyamine content decreased dramatically as well as soluble conjugated polyamine content, while the insoluble ones changed little. Different concentration salt stress increased markedly the ratios of (Spd+Spm)/Put and decreased significantly the total polyamine content in roots and leaves. PAO activities in roots was increased at first and then decreased under NaCl stress, while in leaves the activities changed in opposite direction. It has been noted that the sum of free Spd and Spm (Spd+Spm) content is reversely correlated with PAO activity changes, which suggests that PAO might regulate the free polyamine content, therefore, the contents of the soluble and insoluble conjugated polyamines were affected.

Biogenic Polyamines↗

Effect of a bis(benzyl)polyamine analogue, and DL-alpha-difluoromethylornithine on parasite suppression and cellular polyamine levels in golden hamster during Leishmania donovani infection.

We examined the antileishmanial activity of DL-alpha-difluoromethylornithine (DFMO) and a bis(benzyl)polyamine analogue (MDL 27695; N,N'-bis (3-[(phenyl-methyl)amino] propyl) 1,7-diaminoheptane) in L. donovani infected golden hamsters. DFMO, an enzyme activated irreversible inhibitor of ornithine decarboxylase, the rate limiting enzyme in polyamine biosynthesis, has potent antileishmanial activity. When given as a 2% solution in drinking water 2 days after infection and continued for 4 days, it suppressed liver parasites by 90% and spleen parasites by 99%. Liver parasites were suppressed by 50% and spleen parasites by 77% in L. donovani infected hamsters when treated three times per day for 4 days with a total dose of 60 mg kg-1 body weight of MDL 27695. The polyamine content of the liver and spleen of hamsters was determined after 8 days of L. donovani infection and also after treatment with these drugs. Putrescine and spermidine levels increased significantly in both liver and spleen after Leishmania infection of golden hamsters. Treatment with drugs that inhibit the growth of Leishmania mastigotes in the liver and spleen of golden hamsters also reduced polyamine levels of previously infected golden hamsters. There is a close correlation between the therapeutic activity of the drugs and the polyamine content.

Animals↗

Prevention by L-arginine and polyamines of delayed development and embryotoxicity caused by chemically-induced diabetes in rats.

Diabetes mellitus induction with alloxan at a dose of 110 mg/kg i.p. in rats on Day 4 of pregnancy causes delayed development and resorptions as signs of embryotoxicity. In the present study, the administration of human NPH insulin at doses of 1 to 5 U/d to rats or 1.0 mL of 10 mM L-arginine for 8 d, starting the day following diabetes induction, prevented embryotoxicity and delayed development. Similar results were obtained when the polyamines putrescine, spermidine, or spermine were administered at doses of 1.0 mL of a 10 microM solution to each rat daily. However, even though L-arginine and polyamines prevented adverse effects of severe diabetes on the conceptus, and caused normalization of glucose, beta-hydroxybutyrate levels remained elevated. These results support the hypothesis that the mechanisms of normal and altered development could be mediated by the action of polyamines.

Animals↗

Estrogens and colorectal cancer.

In recent years, several lines of epidemiologic, clinical and experimental evidences have been reported showing that estrogen hormones may be involved in malignant colorectal tumors. The sex differences in site-specific incidence, the increased incidence of colonic cancer in women with breast cancer, the protective effect of increasing parity and the reduced risk among women taking postmenopausal hormones, are all elements suggesting that sex hormones may play a role. Male rats experimentally exposed to the carcinogen dimethylhydrazine, have twice the risk of developing colon cancer and significantly shorter survival times than their female counterparts. Along with the clinical, experimental and epidemiologic findings there are also biologic reasons why estrogen may be protective. Most estrogen action appears to be exerted via the estrogen receptors (ERs) on target cells. ERs have been reported in several solid tumors including gastrointestinal neoplasms such as esophageal, gallbladder, gastric and colorectal cancer. At the end of 1995, a second ER (ER-beta) was cloned from the rat prostate cDNA library and subsequently, the human and mouse homologs. Its demonstration in normal and neoplastic human colorectal tissues and "in vitro" in colonic epithelial cells, has renewed interest in investigating the existence of two ER subtypes. The presence of two ERs could explain the selective actions of estrogens on different target tissues and, particularly, on the gastrointestinal tract. Finally, our studies suggest that estrogens and their receptors play an important role in the growth and progression of colorectal tumors, by interacting with other molecules required for cell proliferation like growth factors and polyamines.

Animals↗

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↗

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↗

Effect of mitoguazone on polyamine oxidase activity in rat liver.

Mitoguazone is a known inhibitor of polyamine biosynthesis through competitive inhibition of S-adenosylmethionine decarboxylase. A recent renewed interest in mitoguazone as an antineoplastic agent prompted us to investigate the effect of the drug on polyamine catabolism in rat liver, since the organ plays an important role in detoxification mechanisms. Thus, the purpose of this work was to evaluate the effect of in vivo mitoguazone administration on polyamine catabolic enzymes. In particular, our interest was directed to the changes in polyamine oxidase activity, since this enzyme has been recently confirmed to exert important functions that until now were underestimated. Mitoguazone administration induced hepatic polyamine oxidase activity starting at 4 h after administration, and the enzyme returned to basal levels 96 h after treatment. The changes in enzyme activity were accompanied by changes in putrescine concentrations, which increased starting at 4 h until 72 h after treatment. We also evaluated the activity of the newly identified spermine oxidase, which was not significantly changed by mitoguazone treatment. Therefore, we hypothesized that the enzyme involved in mitoguazone response of the liver is the polyamine oxidase, which acts on acetylated polyamines as substrate.

Acetyltransferases↗

Inhibition of ornithine decarboxylase by ifenprodil.

Ifenprodil (NMDA receptor antagonist) was tested as an inhibitor of ornithine decarboxylase. It was found that ifenprodil inhibited ornithine decarboxylase activity with the same potency as alpha-difluoromethylornithine, a major inhibitor of ornithine decarboxylase. This result suggests that ifenprodil could target either the polyamine site on the NMDA receptor complex or/and polyamine biosynthesis.

Biogenic Polyamines↗