Increment In Synthesis Research Articles

Training old rats selectively modulates synaptosomal protein synthesis

We have previously shown that the local synthesis of two synaptic proteins of 66.5-kDa and 87.6-kDa is selectively enhanced in male adult rats trained for a two-way active avoidance task. We report here that a comparable but not identical response occurs in 2-year-old male rats trained for the same task. In the latter age group, the local synthesis of the 66.5-kDa protein markedly increases in cerebral cortex, brainstem, and cerebellum, with a somewhat lower increment in synthesis of the 87.6-kDa protein. On the other hand, the newly synthesized 87.6-kDa protein correlates with avoidances and escapes and inversely correlates with freezings in cerebral cortex and brainstem, whereas the correlations of the newly synthesized 66.5-kDa protein remain below significance. These correlative patterns are sharply at variance with those present in trained adult rats. Our data confirm that the local system of synaptic protein synthesis is selectively modulated by training and show that the synaptic response of old rats differs from that of adult rats as reflected in behavioral responses.

Effect of Insulin on High-Glucose Medium-Induced Changes in Rat Glomerular Epithelial Cell Metabolism of Glycoconjugates

We have previously reported that incubation of rat glomerular epithelial cells in vitro for 8 days with 30 mM glucose without insulin results in reduction in the synthesis of a cell layer heparan sulfate proteoglycan (HSPG) species that has hydrodynamic size and antigenic characteristics of glomerular basement membrane HSPG (1994, Arch. Biochem. Biophys 309, 149-159). In these studies, reduction in HSPG synthesis could be attributed either to high-glucose medium or to insulin deficiency. In this study we investigated the effects of insulin replacement on changes in glomerular epithelial cell metabolism of glycoconjugates induced by high-glucose medium. Addition of pharmacologic concentrations of insulin prevented the following changes induced by 30 mM glucose: (a) increment in 35SO 4 incorporation into macromolecules in cell layer and medium, (b) increment in the synthesis of low anionic macromolecules, probably glycoproteins, in both cell layer and medium, (c) increment in synthesis of small-sized glycosaminoglycans ( K av 0.75 on Sephrose CL-4B) associated with the cell layer. Insulin was unable to correct the 30 mM glucose-induced reduction in the synthesis of cell layer HSPG that resembles glomerular basement membrane HSPG. Physiologic concentrations of insulin did not affect any of the changes in glycopeptide metabolism induced by 30 mM glucose, These findings suggest that (a) inhibition of glomerular epithelial cell synthesis of 35SO 4-labeled low anionic macromolecules, probably glycoproteins, may be involved in insulin-induced reversal of glomerular hypertrophy seen in early diabetes, and (b) mechanisms other than insulin lack are involved in reduction in the synthesis of glomerular basement membrane HSPG in diabetic nephropathy.

Regulation of Rat Glomerular Epithelial Cell Proteoglycans by High-Glucose Medium

In diabetic nephropathy the heparan sulfate proteoglycan (HSPG) content of the glomerular basement membrane (GBM) is reduced but the cellular mechanisms involved have not been studied. Glomerular epithelial cells (GEC) are thought to be the source of HSPG present in the GBM. In this study we examined if proteoglycan metabolism of the rat GEC in culture is dysregulated in a metabolic environment simulating diabetes. Following incubation for 8 days with a serum-supplemented medium containing 30 mM glucose and no added insulin, a significant increase in the overall synthesis of 35SO 4-labeled molecules by the GEC was seen compared to control monolayers incubated with medium containing 5 mM glucose and insulin. Ion exchange chromatography revealed that 30 mM glucose did not alter the anionic charge density of proteoglycans, but significantly increased the amount of 35S-labeled low-anionic macromolecules in the medium; mannitol induced similar changes. Sepharose CL-4B chromatography, glycosaminoglycan analysis and immunoprecipitation of control cell layer proteoglycans demonstrated the presence of HSPG of hydrodynamic size, K av 0.4, resembling rat GBM HSPG in size and antigenic nature. Incubation of GEC with 30 mM glucose resulted in a significant reduction (58%) in this HSPG species, an effect not seen with equimolar mannitol. Additionally, 30 mM glucose induced a significant increment in synthesis of a small HS species ( K av 0.71 on Sepharose CL-4B column) present in the cell layer. Our findings suggest that both osmotic and nonosmotic mechanisms are operative in dysregulation of glycopeptide metabolism by high-glucose medium and that reduced synthesis by the GEC may contribute to decreased content of GBM HSPG in diabetic nephropathy.

Adrenocortical steroid hormones, electrolytes, and the disposition of the catecholamines with particular reference to depressive states

Adrenocortical steroid hormones, electrolytes, and catecholamines have each been suggested as having a role in the psychobiology of the affective disorders. In this paper some of the literature relevant to interactions between these systems has been reviewed and the following noted. 1. 1.|There is much evidence from in vivo and in vitro studies indicating that the function of the pituitary-adrenal axis is intimately involved with the synthesis, degradation, and transport of the catecholamines. More specifically, it has been clearly demonstrated that hypophysectomy or adrenalectomy is associated with an increase in the synthesis of catecholamines in tissues other than brain. This increment in synthesis can be reversed by the appropriate replacement treatment. While the effects of alterations of the pituitary-adrenal axis on brain catecholamines have been less intensively studied, the available data indicates that hydrocortisone is involved in NE transport and that adrenalectomy but not hypophysectomy increases the turnover of brain NE. 2. 2.|Deviations from optimal concentrations of Na + and K + or the inhibition of the Mg ++ dependent, Na + - K + activated ATPase result in a decreased uptake of NE, possibly an increased efflux, and an increased rate of synthesis of NE in brain slices. Similar results have been found with a variety of different tissue preparations. Other types of experimental alterations of the ionic environment also are associated with changes in the disposition and synthesis of catecholamines. 3. 3.|Given the demonstrated relationships between the adrenal corticosteroids and catecholamine synthesis, adrenocortical steroids and salt metabolism, and salt concentrations and catecholamine transport and synthesis, a suggested sequence of events whereby the adrenocortical steroid hormones may regulate catecholamine synthesis is presented. 4. 4.|The relevance of the proposed relationship between the adrenocortical steroids, electrolytes, and NE synthesis to human depressive states is discussed.