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N Sekiguchi

Publications and source records attributed to N Sekiguchi.

47 records · Page 3Linked to original sources
PubMed1987

Formation of diacyl and alkylacyl glycerophosphocholine in rabbit alveolar macrophages.

The incorporation of various labeled precursors into alkenylacyl, alkylacyl and diacyl phospholipids in rabbit alveolar macrophages was studied. The incorporation rates of the individual precursors were shown to be quite different among the three subclasses of phospholipids. [3H]Glycerol, [14C]16:0, [14C]18:1, [14C]18:2 and [32P]-orthophosphate were preferentially incorporated into choline glycerophospholipids (CGP), especially into diacyl glycerophosphocholine (GPC), indicating that the de novo synthesis of diacyl GPC is extremely high. Considerable portions of the radioactivities of [14C]16:0, [14C]18:1, [14C]18:2 and [32P]orthophosphate were also found in alkylacyl GPC, the incorporation being higher than or comparable to that in the case of diacyl glycerophosphoethanolamine (GPE). We then examined the activities of cholinephosphotransferase and ethanol-aminephosphotransferase, and found that the activity of cholinephosphotransferase was remarkably high in macrophage microsomes compared with that in microsomes from several other tissues. This suggests that diradylglycerols were preferentially utilized by choline-phosphotransferase, which is consistent with the results obtained for intact cells. We confirmed that a considerably higher amount of diacyl GPC as well as alkylacyl GPC was formed through this enzyme reaction with macrophage microsomes than with brain microsomes. The high formation of alkylacyl GPC could be responsible, at least in part, for the accumulation of this unique ether phospholipid, a stored precursor form of platelet-activating factor in macrophages.

Animals↗
PubMed1987

Chemical and mutagenic properties of alpha-phosphonooxynitrosamines.

The chemical and mutagenic properties of the products of solvolysis of alpha-acetoxynitrosamines in phosphate buffer were investigated. alpha-Acetoxynitrosamines decomposed in two ways: O-acyl fission yielded alpha-hydroxynitrosamines, which decomposed into aldehydes and alcohols, while O-alkyl fission gave a resonance hybrid of alpha-N-nitrosocarbonium and -iminium ions, which was trapped with phosphate and afforded alpha-phosphonooxynitrosamine. Formation of alpha-phosphonooxynitrosamines was dependent on the structure of alpha-acetoxynitrosamines; those with a secondary alpha-phosphonooxy group, including cyclic nitrosamines, were easily formed, while among those with a primary phosphonooxymethyl group, only those with an alkyl group containing a branched alpha-carbon as isopropyl, sec-butyl and tert-butyl were isolated. They were good substrates of alkaline phosphatase and showed a nuclear magnetic resonance spectrum due to the presence of a phosphorus atom. They were decomposed by acid catalysis, and the rate was dependent on the structure. They were directly mutagenic in bacterial tester strains, except for a compound with a tert-butyl group. The activity was similar or stronger in Salmonella typhimurium TA1535 and much weaker in Escherichia coli WP2 and WP2 hcr- than those of alpha-acetoxynitrosamines. Stability in neutral aqueous solution and the strong mutagenicity of alpha-phosphonooxynitrosamines suggested their possible involvement in metabolic activation as a precursor of alpha-hydroxynitrosamines, and also in the organotropic carcinogenicity of N-nitrosodialkylamines as a transport form.

Chemical Phenomena↗
PubMed1985

In vitro metabolism of N-nitrodialkylamines.

The in vitro metabolism of N-nitramines was investigated in order to compare it with that of N-nitrosamines and to elucidate the mode of mutagenic action. N-Nitrodibutylamine (NO2DBA) and N-nitrodiethylamine (NO2DEA) were incubated with liver microsomes and hepatocytes prepared from rats treated with phenobarbital, and the products were analyzed by high-performance liquid chromatography and gas-liquid chromatography. The in vitro metabolic pattern of these nitramines was similar to that of the corresponding nitrosamines, except that N-nitro-N-alkylamines (produced via alpha-hydroxylation) were identified after incubation of the nitrodialkylamines. In the case of NO2DBA, besides N-nitro-N-butylamine, several nitramines produced by omega, omega-1, and omega-2 oxidations were identified as metabolites. NO2DBA and NO2DEA were mutagenic to Escherichia coli WP2 hcr- but not to Salmonella typhimurium TA1535. They were mutagenic only in the presence of hepatic microsomes, whereas their metabolites, N-nitro-N-butylamine and N-nitro-N-ethylamine, were direct mutagens. Thus, N-nitrodialkylamines are also metabolically activated to mutagens through alpha-hydroxylation.

Aniline Compounds↗
PubMed1984

Metabolism of N-nitrodialkylamines.

The in-vitro and in-vivo metabolism of N-nitramines was investigated to compare it with that of N-nitrosamines. N-Nitrodibutylamine and N-nitrodiethylamine were incubated with rat liver microsomes and hepatocytes, and the products were analysed by high-performance liquid chromatography and gas-liquid chromatography. The in-vitro metabolic pattern of these N-nitramines was similar to that of the corresponding N-nitrosamines, except that N-nitromonoalkylamines (produced by alpha-hydroxylation) were isolated and identified after incubation of N-nitrodialkylamines. Seven N-nitramines, including glucuronides, were isolated and identified from urine of rats given N-nitrodibutylamine, produced by omega, omega-1, and alpha oxidations of the N-nitramine. The in-vivo metabolic pattern of N-nitrodibutylamine was also similar to that of N-nitrosodi-n-butylamine except that N-nitromonobutylamine (a product of alpha-hydroxylation) was isolated and identified. N-Nitramines were mutagenic to Escherichia coli WP2 hcr-, but not to Salmonella typhimurium TA 1535. N-Nitrodibutylamine and N-nitrodiethylamine were mutagenic only in the presence of hepatic microsomes, while N-nitromonobutylamine and N-nitromonoethylamine were direct mutagens. Thus, the N-nitrodialkylamine is also metabolically activated to a mutagen through an alpha-hydroxylation.

Animals↗
PubMed1982

Ether phospholipids in guinea pig polymorphonuclear leukocytes and macrophages. Occurrence of high levels of 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine.

Significant proportions of the choline phosphoglycerides (CPG) were found to contain alkyl either-type moieties (e.g., 1-O-alkyl-2-acyl-glycero-3-phosphocholine) in both guinea pig peritoneal exudate polymorphonuclear leukocytes (16.4%) and macrophages (13.5%). High proportions of the ethanolamine phosphoglycerides (EPG) contained alkenyl either moieties in both cells (37.2 and 41.2%), while the proportions of the CPG containing alkenyl moieties and of the EPG containing alkyl moieties were shown to be small. The either phospholipid composition as well as the fatty chain profiles of these two types of cells had relatively similar patterns. However, the fatty chains at the 1- and 2-positions for alkenyl either, alkyl ether and diacyl phosphoglycerides showed considerable differences. The amount of 16:0 at the 1-position was higher in alkyl compounds than that in diacyl compounds of the CPG. This was also the case in either-containing and diacyl EPG. The most predominant fatty acids at the 2-position was 18:2, in each lipid class, except for the alkenyl CPG. The amounts of 20:4 and other polyunsaturated fatty acids were low in every lipid class, though ether compounds contained higher amounts of 20:4 than diacyl compounds, particularly for EPG.

Animals↗
PubMed1982

Chemistry and mutagenicity of alpha-hydroxy nitrosamines.

N-Nitroso-N-(hydroxymethyl)alkylamines, which are key intermediates in the metabolic activation of nitrosamines having a methyl group, were synthesized and their chemical and mutagenic properties were examined. Six N-nitroso-N-(hydroxymethyl)alkylamines (alkyl = methyl, ethyl, n-propyl, n-butyl, sec-butyl, tert-butyl) were prepared by the deoxygenation of N-nitroso-N-(hydroperoxymethyl)alkylamines. Their stability in aqueous solution was highly dependent on pH, being stable in acidic media, but unstable in neutral or alkaline media. The structure also exerted a profound effect on the stability. Thus a branched alkyl group accelerated the decomposition, although compounds with a normal alkyl group showed a similar response to the change of pH. The alkylating activity of the compounds toward deoxyguanosine and thymidine was demonstrated, and was dependent on the reaction solvent used. The overall alkylating activity was found to be highest with the compound ultimately yielding a methylating agent, while a more selective alkylation towards the oxygen, compared to the nitrogen, was observed with the ethylating, propylating and butylating species. Reactions with cysteine and histidine were also observed. A potent mutagenic effect of the N-nitroso-N-(hydroxymethyl)alkylamines was demonstrated in Salmonella typhimurium TA1535 and Escherichia coli WP2 and WP2 hcr-, in the absence of the S9 mix. A good correlation of the activities of the N-nitroso-N-dialkylamines and the N-nitroso-N-(hydroxymethyl)alkylamines with the same alkyl group was demonstrated.

Alkylation↗
PubMedDate not supplied

Reduced expression of a novel peptide, prostacyclin-stimulating factor, in the kidneys of streptozotocin-induced diabetic rats.

Prostacyclin (PGI2) produced by vascular endothelial cells (ECs) is a potent vasoactive prostanoid involved in maintenance of vessel wall homeostasis. Reduced PGI2 synthesis by vascular ECs could be a mechanism of pathogenesis in the development of vascular lesions such as diabetic angiopathy. Recently, we purified and cloned a novel bioactive peptide, PGI2-stimulating factor (PSF), which stimulates PGI2 production by vascular ECs. PSF may act on vascular ECs in a paracrine and/or autocrine fashion to regulate PGI2 synthesis. Decreased PSF production in the vessel wall may result in an imbalance of prostanoid synthesis, leading to the development of vascular lesions such as diabetic angiopathy. Our immunohistochemical study demonstrated that PSF is located in vascular resident cells such as vascular smooth muscle cells (SMCs) and ECs, as well as in bronchial SMCs. Moreover, PSF mRNA was found to be expressed in various tissues in Wistar rats, particularly in the kidneys and lungs. The present study demonstrated that streptozotocin (STZ)-induced diabetic rats showed less PSF mRNA expression in the kidneys (PSF mRNA/28S rRNA ratio; STZ versus control; 1.7+/-0.2 versus 2.5+/-0.2, p < 0.05) and reduced immunohistochemical staining for PSF in arteries in the kidney. However, in the lungs, there were no changes in tissue PSF mRNA expression (STZ versus control; 10.9+/-0.9 versus 11.5+/-1.0, NS) or in the extent of PSF staining in bronchial SMCs of STZ-induced diabetic rats. These findings suggest that decreased expression of PSF in renal vessels of STZ-induced diabetic rats may cause an imbalance of prostanoid synthesis, leading to the development and progression of vascular damage in the kidney.

Animals↗