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Biomedical subjects

C A Manen

Publications and source records attributed to C A Manen.

16 recordsLinked to original sources
PubMed1983

Ornithine decarboxylase inhibitors and fetal growth retardation in mice.

Putrescine (PUT) and the putrescine analogues, 1,3-diaminopropane (DAP) and 1,6-diaminohexane (DAH), were administered to pregnant female mice during the time of maximal fetal ornithine decarboxylase (ODC) activity, days 10-14 of gestation. Such treatment resulted in an inhibition of fetal ODC activity, as measured 2 hours later, and a proportional decrease in fetal weight, as measured on day 18 of gestation. The order of effectiveness for these compounds was DAP greater than DAH greater than PUT. Neither DAP nor DAH nor PUT were fetocidal nor maternally lethal under the treatment regimen employed. The generality of the effect of these compounds, i.e., the retardation of fetal growth and the lack of gross malformations, is consistent with the hypothesis that they are interfering with a primary process, probably protein synthesis. The restricted time span of effectiveness implies that these compounds are specific inhibitors of ODC and that decreased ODC activity is producing an effect on growth.

Animals↗
PubMed1982

Posttranslationally modified ornithine decarboxylase may regulate RNA polymerase I activity.

Purified ornithine decarboxylase (EC 4.1.1.17, ODC) transamidated with four putrescine moieties on four glutamine residues through the action of transglutaminase (EC 2.3.2.13, TGase) purified from guinea pig liver, when added to isolated rat liver nuclei, stoichiometrically increased the activity of RNA polymerase I (EC 2.7.7.6). The increase was relative to the pmoles of purified conjugated ODC added to the reaction and could be reinitiated after the reaction had plateaued by the further addition of ODC-putrescine conjugate. The kinetics of the reaction suggest that the ODC-putrescine conjugate was not reused but degraded after each initiation. Otherwise, the rapid plateau would not be observed. The repeated addition of 278 pmoles of purified ODC-putrescine conjugate to rat liver nuclear preparations containing 200 micrograms total protein consistently stimulated the incorporation of 600-700 pmoles UMP/mg protein. We suggest that ODC transamidated by its product putrescine may be the posttranslationally modified 65,000 Mr protein which has been reported by several laboratories to serve as a labile subunit of RNA polymerase I.

Animals↗
PubMed1982

Altered activation of rat hepatic cyclic AMP-dependent protein kinases with increasing age.

The activity ratio of hepatic cyclic AMP-dependent protein kinase has been found to change with increasing age in male, Long-Evans rats. In rats 35 days old (135 g), the activity ratio (cyclic AMP-dependent protein kinase activity measured in the absence and presence of exogenous cyclic AMP) was 0.76, it increased to 0.92 in rats 75 days old (315 g) and to 0.98 in rats 305 days old (646 g). This change in the activity ratio seems to correlate with the ability of aging animals to respond to a stimulus, and may be a primary mechanism in the biochemistry of aging.

Aging↗
PubMed1976

Altered polyamine metabolism in the PRO/Re strain of inbred mice.

The PRO/Re strain of inbred mice are characterized by abnormally high concentrations of proline in both blood (hyperprolinaemia) and urine (prolinuria). They excrete increased amounts of polyamines in their urine. Male PRO/Re mice excreted putrescine at 175% and spermidine at 300% the amount of male C57BL/6J controls. Female PRO/Re mice excreted putrescine at 115% and spermidine at 150% of the amount in the urine of female controls. Examination of the enzymes involved in polyamine biosynthesis revealed that ornithine decarboxylase, the initial enzyme in the polyamine-biosynthetic pathway, was increased by 150% in the kidneys and by 100% in the liver of male PRO/Re mice. There was no significant difference between PRO/Re and C57BL/6J male mice for either putrescine- or spermidine-stimulated S-adenosylmethionine decarboxylase activity. Female PRO/Re mice showed no significant difference from female C57BL/6J mice for any of the enzymes examined. When the concentrations of the polyamines in the tissues of the PRO/Re mice were determined, spermidine and spermine concentrations in the kidneys of the male PRO/Re mice were twice those of the controls. Spermidine concentration in the livers of both male and female PRO/Re mice was approx. 130% that of the controls. Polyamine concentrations in the brains were similar in controls and mutants. The increased polyamine biosynthesis and excretion in the PRO/Re mutant mice may be a mechanism to decrease the extent of proline accumulation.

Adenosylmethionine Decarboxylase↗
PubMed1976

Polyamine synthesis in liver and kidney of flounder in response to methylmercury.

The effect of methylmercury administration on polyamine synthesis was studied in the liver and kidney of the winter flounder (Pseudopleuronectes americanus). A single injection of methylmercury resulted in five- and sevenfold elevations of ornithine decarboxylase activity in the liver and kidney within 15 and 45 h, respectively. There were elevations of both putrescine- and spermidine-stimulated S-adenosylmethionine decarboxylase activities (approximately 1.5-fold) in both tissues. Evaluation of the polyamine accumulation patterns in these tissues indicated that in the liver all three polyamines increased in concentration until 48 h and then decline. In the kidney, the concentration of putrescine increased steadily until it was 200% of control at 72 h and then declined. Spermidine concentration decreased throughout the time studied and was 17% of control at 1 wk. There was no significant change in the concentration of spermine throughout the period studied. The changes in the polyamine pools and in the activities of the polyamine biosynthetic enzymes after methylmercury administration are consistent with an involvement of the polyamines in the recovery phase to a toxic dose of methylmercury.

Adenosylmethionine Decarboxylase↗