The influence of insulin and glucagon on hydroxymethylglutaryl coenzyme A reductase activity in rat liver.
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Biomedical subjects
Publications and source records attributed to B Hamprecht.
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The accumulation of endogenous adenosine 3':5'-cyclic phosphate (cAMP) and of [(14)C]cAMP, derived from nucleotides labeled by prior incubation of cells with [(14)C]adenine, has been investigated in four glial cell lines from rats. The following results are similar to data reported for brain slices: (i) rat glial cells contain a system that readily incorporates [(14)C]adenine into nucleotides that serve as precursors for cAMP. (ii) norepinephrine stimulates accumulation of both [(14)C]cAMP and endogenous cAMP, and (iii) the phosphodiesterase inhibitors, papaverine and isobutylmethylxanthine, are effective in enhancing the stimulatory effect of norepinephrine. In contrast to results reported for brain slices, histamine, veratridine, and adenosine, the purine either alone or with a biogenic amine, do not cause an enhanced accumulation of cAMP in rat glial cells, and repetitive accumulations of cAMP can be elicited during a series of restimulations of the cells with norepinephrine. The magnitude of the accumulation of cAMP elicited by the catecholamine decreases markedly by the fifth restimulation in the absence of, but only slightly in the presence of, papaverine. In glial cells, a large portion of the [(14)C]adenine is incorporated into intracellular compounds that do not serve as precursors of [(14)C]cAMP.
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To obtain information on the glutathione metabolism of microglial cells, the content of glutathione and activities of enzymes involved in the defense against peroxides were determined for microglia-rich cultures from rat brain. These cultures contain approximately 90% microglia cells as determined by immunocytochemical staining for glial markers, by the phagocytosis activity of the cells and by the production of superoxide after stimulation of the cells with phorbolester. For these cultures, a glutathione content of 41.2 +/- 11.2 nmol/mg protein and a specific activity of glutathione reductase of 15.2 +/- 3.2 nmol/(min x mg protein) were determined. These values are significantly higher than those found for astroglial or neuronal cultures. In addition, with 68.7 +/- 23.5 nmol/(min x mg protein), the specific activity of glutathione peroxidase in microglial cultures was 78% higher than in cultured neurons. The specific catalase activity of microglial cultures was less than 40% that of astroglial or neuronal cultures. Microglial cultures contain only marginal amounts of oxidized glutathione. However, on application of oxidative stress by incubation of microglial cultures with hydrogen peroxide or with the superoxide-producing hypoxanthine/xanthine oxidase system, cellular glutathione was rapidly oxidized. These results demonstrate that microglial cells have a prominent glutathione system, which is likely to reflect the necessity for self-protection against reactive oxygen species when produced by these or surrounding brain cells.