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Biomedical subjects

S Varon

Publications and source records attributed to S Varon.

At least 217 records · Page 12Linked to original sources
PubMed1977

Nerve growth factor action on membrane permeation to exogenous substrates in dorsal root ganglionic dissociates from the chick embryo.

An experimental system has been described, in previous studies, where the ability of chick embryo dorsal root ganglionic cells to incorporate radiouridine into RNA declines in the absence of nerve growth factor (NGF), and is promptly restored by delayed supply of the factor. Following these early and fully reversible events, further NGF deprivation causes progressive irreversible damage. The early decline in RNA labeling and its reversion by NGF are accompanied by similar changes in the accumulation of acid-soluble radioactivity from the exogenous radiouridine substrate. In the present study, it is shown that the NGF-dependent accumulation of "soluble" radiomaterials is independent from, and responsible for, the NGF-dependent alterations in RNA labeling. Both changes are measurable with labeled cytidine and guanosine, as well as uridine, and in all cases accumulation of acid-precipitable and acid-soluble radioactivities are strictly proportional to each other. The acid-soluble responses to NGF are not prevented by actinomycin D or cycloheximide treatments, demonstrating that they require neither ongoing syntheses of RNA or protein nor prior effects of NGF on them. Chromatography of acid-soluble radiopools showed that the NGF-dependent increase was not due to a distortion in the intracellular phosphorylation of uridine; but involved corresponding increases in all the radiouridine derivatives including UTP. The time patterns of the acid-soluble response were comparable to those of the RNA labeling response, and maximal NGF effects occurred within minutes of its presentation. Finally, 2-deoxyglucose and a-aminoisobutyric acid, but not leucine, showed NGF-dependent accumulation patterns similar to those of the 3 nucleosides. It is proposed that regulation of selected membrane permeation properties could be the primary process through which NGF exerts its trophic role.

Adenosine↗
PubMed1975

Nerve growth factor-induced rapid activation of RNA labeling in dorsal root ganglionic dissociates from chick embryos.

Dorsal root ganglionic cells, from 8-day chick embryo, undergo anabolic declines when incubated in vitro without Nerve Growth Factor (NGF) or other supportive agents. To determine whether the decline could be opposed by delayed administration of the NGF, cells were incubated without the factor for varying times, then supplies with it and tested periodically with pulses of radiouridine or radioleucine. The decline in RNA labeling was actually reversed by a delayed addition of NGF, and the effect was fully elicited within less than 10 min from the treatment. With delays up to 6 hr, this rapid activation by NGF fully restored the incorporation rate exhibited by fresh cells or by cells continuously incubated with NGF. From the hour 8 on, the NGF-induced activation of RNA labeling fell progressively shorter of restoring maximal performance until, by 18 hr, it was no longer significant. The residual (irreversible) decline in RNA labeling, starting after 6 hr, developed with a time pattern coincidental with that of the irreversible decline in protein labeling also displayed by those untreated cells, and similar to the appearance of RNA degradation and the acceleration of protein degradation. All four such "degenerative" events were fully prevented by NGF when administered with delays shorter than 6 hr, and only interrupted (or delayed) by NGF delivered at later times. Additional experiments revealed that, over the first 6 hr, NGF also prevented or reversed a decline in TCA-soluble radioactivity of the cells, an effect which was not blocked by actinomycin D. This rapid increase of soluble radioactivity could be responsible for the rapid activation of RNA labeling and may also be involved in the prevention by NGF of the later developing degenerative events.

Animals↗
PubMed1975

Dynamic, temperature-sensitive association of 125-i-nerve growth factor in vitro with ganglionic and non-ganglionic cells from embryonic chick.

125-I-NGF was found to associate with embryonic chick dorsal root ganglia (DRG) through two processes. A time-saturable process included the binding of NGF to surface receptors with an apparent affinity constant in the range of 10(-7)M minus 1 and at a level of 4 f moles/mug tissue protein. The second process was time-linear, temperature-sensitive, and included both bound and non-competable NGF. While metabolic inhibitors had little effect, histone and insulin considerably increased the uptake. A comparison of 125-I-NGF and 125-I-peroxidase uptake suggested that the time-linear uptake of 125-I-NGF must include only bound NGF and incubation medium. Sequestration of the proteins taken up was indicated by the lack of release of radiolabeled material at 4 degrees C, even in the presence of native proteins. All these characteristics are consistent with an interpretation that DRG cells can take up NGF and other proteins by a pinocytotic process. Similar NGF binding and uptake properties were found to occur in cells from a variety of other embryonic chick tissues.

Animals↗