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O Z Sellinger

Publications and source records attributed to O Z Sellinger.

At least 37 records · Page 2Linked to original sources
PubMed1981

Effect of methionine sulfoximine on methylation of guanine residues in astroglial transfer ribonucleic acids.

Culture-grown astrocytes derived from 3-day-old rat brain were incubated in the presence of [3H]guanosine and of the convulsant agent L-methionine-dl-sulfoximine (MSO). The resulting [3H]tRNA was purified from control and MSO-exposed cells at several time points during the incubation and was hydrolyzed to [3H]guanine and four [3H]methyl guanines which were separated by high pressure liquid chromatography. Three of the four [3H]methyl guanines were more highly labeled in the [3H]tRNA of the MSO-exposed cells, relative to that of the control cells throughout the entire incubation period. The findings extend to cultured astrocytes, the stimulatory effect of MSO on the methylation of neural tRNA guanines, previously observed both in vitro using [14C]S-adenosyl-L-methionine and in vivo using [methyl-3H]L-methionine.

Animals↗
PubMed1981

Decreased transmethylation of biogenic amines after in vivo elevation of brain S-adenosyl-l-homocysteine.

The ability of S-adenosyl-L-homocysteine (AdoHcy) to inhibit biologic transmethylation reactions in vitro has led us to explore the possibility of pharmacologically manipulating AdoHcy levels in vivo and examining the consequences of these alterations on the transmethylation of some biogenic amines. Swiss-Webster mice were injected intraperitoneally with different doses of adenosine (Ado) and D, L-homocysteine thiolactone (Hcy) and were killed at various times thereafter. S-Adenosyl-methionine (AdoMet) and AdoHcy concentrations were determined by using a modified isotope dilution-ion exchange chromatography-high pressure liquid chromatography technique sensitive to less than 10 pmol. Increasing doses of Ado + Hcy (50-1000 mg/kg of each) produced a dose-related increase in blood, liver, and brain AdoHcy levels. At a dose level of 200 mg/kg Ado + Hcy, AdoHcy levels were markedly elevated, with minimal concomitant perturbations of AdoMet. This elevation was maximal 40 min after giving Ado + Hcy, returning to control values within 6 h. Ado + Hcy treatment resulted in decreased activities of catechol-O-methyltransferase, histamine-N-methyltransferase, and AdoHcy hydrolase in vitro. The cerebral catabolism of intraventricularly administered [(3)H]histamine (HA) was decreased in a dose-related manner by Ado + Hcy treatment as evidenced by higher amounts of nonutilized [(3)H]HA in brain, concurrent decreases in [(3)H]methylhistamine formation, and decreases in the transmethylation conversion index. Steady state levels of HA also showed dose-related increases after Ado + Hcy treatment. It is concluded that injections of Ado + Hcy can markedly elevate AdoHcy levels in vivo, which can, in turn, decrease the rate of transmethylation reactions.

Adenosine↗
PubMed1981

Decreased cerebral catabolism of [3H]histamine in vivo after S-adenosylmethionine administration.

Administration of S-adenosyl-L-methionine (SAM) (200 mg/kg) to adult mice significantly elevated its cerebral levels while the steady-state levels of histamine (HA) and S-adenosyl-L-homocysteine remained unaltered. [3H]HA (1 microCi/10 microliters) was injected intraventricularly (i.vt.) 20 sec, 2, 5, 10 or 20 min prior to sacrifice (1 hr after SAM) and brains were analyzed for [3H]HA, [3H]methylhistamine (MeHA) and [3H]methylimidazoleacetic acid. Brains of SAM-treated mice contained more [3H]HA than vehicle-treated controls at 20 sec, 2, 5 and 10 min (22, 35, 52 and 25%, respectively). [3H]MeHA levels were lower than controls at 20 sec, but higher at 2 and 5 min. Fifteen minutes after i.vt. [3H]histidine, brains of SAM-treated mice contained 47% more [3H]HA and 39% more [3H]MeHA (compared to controls) while [3H]histidine and [3H]methylimidazoleacetic acid levels remained unchanged. SAM treatment had no effect on the activity of cerebral histamine-N-methyltransferase, S-adenosyl-L-homocysteine hydrolase and monoamine oxidase type A (substrate 5-hydroxytryptamine) when tested in vitro, while monoamine oxidase B (substrate phenylethylamine) activity was significantly decreased. In vitro, SAM had no effect on monoamine oxidase A or B. The findings demonstrate that, unexpectedly, the rate of catabolism of HA to MeHA is significantly decelerated in brains containing elevated levels of SAM.

Animals↗
PubMed1980

Cerebellar tRNA methyltransferases: a developmental study.

Developmental patterns of homologous and heterologous tRNA methylation by cerebellar tRNA methyltransferases are described. The study revealed that: (a) homologous tRNA methylation results in the predominant formation of N2-methylguanine and 1-methyladenine; (b) tRNA methyltransferase of bulk-isolated Purkinje and granule cells methylate E. coli tRNAglu2 in vitro in a characteristic manner, and (c) the methylation of 8-day-old cerebellar, cortical and hepatic tRNA in vivo yields tRNAs containing different proportions of methylated bases. The findings suggest that the presumably cell-specific populations of cerebellar tRNA methyltransferases continue to alter their substrate recognition characteristics up to and beyond the first month of post-natal life.

Aging↗
PubMed1980

Differences in activity in cerebral methyltransferases and monoamine oxidases between audiogenic seizure susceptible and resistant mice and deermice.

The specific acitivity of cerebral histamine N-methyltransferase (HMT) was significantly lower in the audiogenic seizure-susceptible (SS) 21-day old DBA/2J mouse when compared to the non-susceptible 70-day old DBA/2J mouse but not when compared to the seizure resistant (SR) C57B1/6J mouse at 21 days of age. There was no significant difference between the two strains at 70 days of age. The lower HMT specific activity was also observed in a SS mutant of the deermouse Peromyuscus maniculatus, relative to the SR, wild-type animal. The activity of cerebral catechol-O-methyltransferase (COMT) was significantly lower in the DBA/2J mice relative to the C57B1/6J at 21 and 70 days while, in Peromyscus, it was higher in the SS mutant than in the SR animal. The activity of MAO, B was lower in the 21-day old, relative to the 70-day old DBA/2J and the 21-day old C57B1/6J mice. There were no differences in MAO A or B between SS and SR Peromyscus. The findings raise the possibility that cerebral methylation may operate at characteristic rates in SS animals.

Acoustic Stimulation↗
PubMed1980

The biosynthesis of transfer ribonucleic acid in the developing rat brain and in cultured glial cells.

The biosynthesis of tRNA was investigated in cultured astroglial cells and the 3-day-old rat brain in vivo. In the culture system astrocytes were grown for 19 days and were then exposed to [3H]guanosine for 1.5-7.5 h; 3-day-old rats were injected with [3H]guanosine and were killed 5-45 min later. [3H]tRNA was extracted, partially purified, and hydrolyzed to yield [3H]guanine and [3H]methyl guanines. The latter were separated from the former by high performance liquid chromatography and their radioactivity determined as a function of the time of exposure to [3H]guanosine. The findings indicate that labeling of astrocyte tRNA continued for 7.5 h and was maximal, relative to total RNA labeling, at 3 h, while in the immature brain tRNAs were maximally labeled at 20 min after [3H]guanosine administration. The labeling pattern of the individual methyl guanines differed considerably betweren astrocyte and brain tRNAs. Thus, [3H]1-methylguanine represented up to 35% of the total [3H]methyl guanine radioactivity in astrocyte [3H]tRNA, while it became only negligibly labeled in brain [3H]tRNA. Conversely, brain [3H]tRNA contained more [3H]N2-methylguanine than did astrocyte [3H]tRNA. Approximately equal proportions of [3H]7-methylguanine were found in the [3H]tRNAs of both neural systems. The [3H]methylguanine composition of brain [3H]tRNA was followed through several stages of tRNA purification, including benzoylated DEAE-cellulose and reverse phase chromatography (RPC-5), and differences were found between the [3H]methylguanine composition of RPC-5 fractions containing, respectively, tRNAlys and tRNAphe. The overall results of this study suggest that developing brain cells biosynthesize their particular complement of tRNAs actively and in a cell-specific manner, as attested by the significant differences in the labeling rates of their methylated guanines. The notion is advanced that cell-specific tRNA modifications may be a prerequisite for the successful synthesis of cell-specific neural proteins.

Aging↗
PubMed1979

The postnatal methylation of transfer ribonucleic acid in brain. Evidence for the methylation of precursor transfer ribonucleic acid.

Incubation of 3-day-old rat brain with L-[methyl-3H]methionine resulted in the rapid labeling of low-molecular-weight cytoplasmic RNA. Electrophoresis in 15% polyacrylamide gels provided evidence for the methylation of precursor tRNA molecules, and high-performance liquid chromatography demonstrated N2-methylguanine to be the predominant methylated base formed during the first 2 min of labelling.

Animals↗
PubMed1979

Age-dependent changes in the specificity of tRNA methyltransferases in the cerebellum of the icteric and nonicteric Gunn rat.

The activity of tRNA methyltransferases present in the cerebellum of 6- and 21-day-old nonicteric and icteric Gunn rats was compared using purified E. coli tRNAs as substrates. At 6 days the tRNA methyltransferases of the icteric animals were significantly more effective in methylating tRNAGlu2 and tRNAPhe than were those of their nonicteric counterparts. This relationship reversed itself at 21 days. The action of the tRNA methyltransferases from the 6-day-old icteric animals led to higher proportions of 1-methyladenine in tRNAGlu2 and tRNAPhe than were obtained using the corresponding enzymes of the nonicteric animals. The proportion of N2-methylguanine was also higher, yet only in tRNAfMet and not in tRNAPhe. The study reveals much more extensive fluctuations in the activity and in the substrate recognition specificity among the cerebellar tRNA methyltransferases of the icteric than among those of the nonicteric controls during the crucial 6--21 day period of cerebellar development.

Aging↗