Biomedical subjects

G R Jackson

Publications and source records attributed to G R Jackson.

32 records · Page 2Linked to original sources

PubMed1994

Effects of nerve growth factor on catalase and glutathione peroxidase in a hydrogen peroxide-resistant pheochromocytoma subclone.

Stepwise selection in increasing H2O2 concentrations was used to obtain a PC12 cell variant designated HPR. This variant was stably resistant to H2O2 as compared with the parental PC12 cell line. HPR cells responded to nerve growth factor (NGF) by further enhancing H2O2 resistance. This variant was subcloned by limiting dilution to obtain the line referred to as HPR-C, which was stably resistant to H2O2 toxicity and retained NGF responses, including morphologic changes and further reduction of H2O2 toxicity. When compared with the parental PC12 line, the HPR-C subclone did not have higher levels of catalase or glutathione peroxidase (GSH Px) activity or mRNA expression (as assessed by PCR analysis of cDNA reverse transcribed from total cellular RNA). HPR-C cells retained the ability to respond to NGF treatment by increasing catalase and GSH Px activity and expression. These data suggest that the protective effects of conditioning lesions, unlike those of neurotrophins, are in part independent of changes in the activity or expression of antioxidant enzymes.

Adrenal Gland Neoplasms↗

PubMed1994

Effects of nerve growth factor on glutathione peroxidase and catalase in PC12 cells.

Nerve growth factor (NGF) is a member of the neurotrophin family and is required for the survival and maintenance of peripheral sympathetic and sensory ganglia. In the CNS, NGF regulates cholinergic expression by basal forebrain cholinergic neurons. NGF also stimulates cellular resistance to oxidative stress in the PC12 cell line and protects PC12 cells from the toxic effects of reactive oxygen species. The hypothesis that NGF protection involves changes in antioxidant enzyme expression was tested by measuring its effects on catalase and glutathione peroxidase (GSH Px) mRNA expression in PC12 cells. NGF increased catalase and GSH Px mRNA levels in PC12 cells in a time- and dose-dependent manner. There was also a corresponding increase in the enzyme activities of catalase and GSH Px. Thus, NGF can provide cytoprotection to PC12 cells by inducing the free radical scavenging enzymes catalase and GSH Px.

Animals↗

PubMed1994

Neurotrophin regulation of energy homeostasis in the central nervous system.

Our hypothesis is that one cause of neuronal cell death and shrinkage in the aged central nervous system is an inability of neurons to maintain oxidant homeostasis in the face of increased levels of reactive oxygen species, decreased endogenous antioxidants, and impaired energy metabolism associated with physiological senescence, Alzheimer's, and Parkinson's diseases. Since treatment with nerve growth factor (NGF) reverses behavioral impairments in aged rats and stimulates cholinergic activity in the basal forebrain, while brain-derived neurotrophic factor appears to play a similar role in the striatum, we propose that neurotrophin-mediated cell-sparing reflects effects on oxidant homeostasis. Neurotrophins may play a similar cell-sparing role in hypoxic/ischemic injury to the nervous system, which also is mediated in part by reactive oxygen species. The degradation of one such species, H2O2, is catalyzed by catalase and glutathione peroxidase (GSH Px). The activity of the latter enzyme is dependent on glutathione reductase and the availability of NADPH for regeneration of reduced GSH. The GSH redox cycle is also regulated by enzymes of the hexose monophosphate shunt. NGF protects PC12 cells from H2O2 injury by stimulating the synthesis of antioxidant enzymes including catalase, GSH Px, glucose-6-phosphate dehydrogenase, and gamma-glutamylcysteine synthetase, the rate-limiting enzyme for glutathione synthesis. NGF also enhances recovery from the NAD+ losses occurring as a consequence of H2O2 treatment.

Animals↗

PubMed1992

Nerve growth factor effects on pyridine nucleotides after oxidant injury of rat pheochromocytoma cells.

Neurotrophic factors regulate neuronal survival and neurite growth in development and following injury. Oxidative stress produced in neurons as a consequence of primary injury, or during reperfusion following ischemia, may contribute to cell death. Here, the effects of nerve growth factor (NGF) on the response to H2O2 injury were examined in the PC12 rat pheochromocytoma cell line. Specifically, the effect of NGF on cell viability after H2O2 injury was measured. Pretreatment with NGF enhanced survival after H2O2 treatment, as measured by Trypan blue dye exclusion, radiolabeled amino acid incorporation, tetrazolium salt reduction, or cytoplasmic enzyme release. One early event associated with H2O2 treatment was a rapid decrease in NAD+. Although initial decreases in NAD+ levels were similar in control and NGF-treated cells, the latter recovered more rapidly and extensively. The decline in total NAD observed after NGF treatment was almost equal in magnitude to the measured increase in NADP. Inhibition of poly(ADP-ribose) polymerase also enhanced viability following H2O2 injury. Treatment with both NGF and an inhibitor of this enzyme resulted in a greater reduction of H2O2 toxicity than was observed with either agent alone. These data suggest that NGF protection is multifactorial and that a significant component of the NGF effect is due to its regulatory role in the metabolism of pyridine nucleotides.

Animals↗

PubMed1992

Stimulation of nerve growth factor receptors in PC12 by acetyl-L-carnitine.

Acetyl-L-carnitine (ALCAR) prevents some deficits associated with aging in the central nervous system (CNS), such as the aged-related reduction of nerve growth factor (NGF) binding. The aim of this study was to ascertain whether ALCAR could affect the expression of an NGF receptor (p75NGFR). Treatment of PC12 cells with ALCAR increased equilibrium binding of 125I-NGF. ALCAR treatment also increased the amount of immunoprecipitable p75NGFR from PC12 cells. Lastly, the level of p75NGFR messenger RNA (mRNA) in PC12 was increased following ALCAR treatment. These results are in agreement with the hypothesis that there is a direct action of ALCAR on p75NGFR expression in aged rodent CNS.

Acetylcarnitine↗

PubMed1992

Dexamethasone blocks nerve growth factor induction of nerve growth factor receptor mRNA in PC12 cells.

Glucocorticoids and nerve growth factor (NGF) have been shown to have antagonistic effects on chromaffin cells in vivo. Here we determined the effect of the synthetic glucocorticoid, dexamethasone, on levels of mRNA for the nerve growth factor receptor (NGFR) in rat PC12 pheochromocytoma cells. Following administration of dexamethasone (1 microM) there is a decline in NGFR mRNA expression. More importantly, administration of dexamethasone appears to block the NGF-mediated induction of NGFR when both agents are administered simultaneously. These data support the hypothesis that glucocorticoids and NGF act in opposition in determination of the phenotype of chromaffin cells.

Animals↗

PubMed1991

Acetyl-L-carnitine enhances the response of PC12 cells to nerve growth factor.

We have demonstrated that treatment of rat pheochromocytoma (PC12) cells with acetyl-L-carnitine (ALCAR) stimulates the synthesis of nerve growth factor receptors (NGFR). ALCAR has also been reported to prevent some age-related impairments of the central nervous system (CNS). In particular, ALCAR reduces the loss of NGFR in the hippocampus and basal forebrain of aged rodents. On these bases, a study on the effect of NGF on the PC12 cells was carried out to ascertain whether ALCAR induction of NGFR resulted in an enhancement of NGF action. Treatment of PC12 cells for 6 days with ALCAR (10 mM) stimulated [125I]NGF PC12 cell uptake, consistent with increased NGFR levels. Also, neurite outgrowth elicited in PC12 cells by NGF (100 ng/ml) was greatly augmented by ALCAR pretreatment. When PC12 cells were treated with 10 mM ALCAR and then exposed to NGF (1 ng/ml), an NGF concentration that is insufficient to elicit neurite outgrowth under these conditions, there was an ALCAR effect on neurite outgrowth. The concentration of NGF necessary for survival of serum-deprived PC12 cells was 100-fold lower for ALCAR-treated cells as compared to controls. The minimal effective dose of ALCAR here was between 0.1 and 0.5 mM. This is similar to the reported minimal concentration of ALCAR that stimulates the synthesis of NGFR in these cells. The data here presented indicate that one mechanism by which ALCAR rescues aged neurons may be by increasing their responsiveness to neuronotrophic factors in the CNS.

Acetylcarnitine↗

PubMed1991

Antioxidant effect of retinoic acid on PC12 rat pheochromocytoma.

Retinoic acid is a naturally occurring metabolite of vitamin A that influences the differentiation of a variety of neural cells in vitro. In the LA-N-1 human neuroblastoma line, retinoic acid treatment increases the binding of nerve growth factor (Bmax). The purpose of this study was to examine the effects of retinoic acid on PC12 rat pheochromocytoma, a neural crest-derived cell line that can be induced to express a sympathetic neuroblast-like phenotype by nerve growth factor treatment. In contrast to the differentiating effects of nerve growth factor, retinoic acid treatment of PC12 cells had a negligible effect on cellular morphology. However, treatment with retinoic acid enhanced the survival of PC12 cells following oxidative injury generated by H2O2 treatment in a manner that is qualitatively similar to that observed after nerve growth factor treatment. Also, there was an increase in 125I-nerve growth factor binding activity in solubilized PC12 membrane preparations derived from retinoic acid-treated PC12 cells. These data suggest that retinoic acid may play a role in neuronal development and in neuronal injury by stimulating the ability of neurons to cope with oxidative stress and/or by enhancing neuronal responsiveness to trophic factors such as the nerve growth factor.

Adrenal Gland Neoplasms↗

PubMed1990

Role of nerve growth factor in oxidant-antioxidant balance and neuronal injury. I. Stimulation of hydrogen peroxide resistance.

The nerve growth factor protein (NGF) regulates neuronal cell death during the development of embryonic sensory and sympathetic neurons in the peripheral nervous system (PNS). NGF protects the rat pheochromocytoma line PC12, a useful model of NGF responsive peripheral neurons, from hydrogen peroxide, which interacts with ferrous iron to generate hydroxyl radicals. Exogenous catalase provides protection, whereas superoxide dismutase (SOD) has no effect on neuronal survival when PC12 cells are challenged with hydrogen peroxide. NGF treatment of PC12 cells increases the activity of catalase. NGF protection from hydrogen peroxide is partially abolished by aminotriazole (Az), a low molecular weight catalase inhibitor. Taken together, these data are consistent with the hypothesis that NGF protects from peroxidative events and consequent cell death via an induction of free radical detoxifying mechanisms, such as catalase activity.

Animals↗

PubMed1990

Role of nerve growth factor in oxidant-antioxidant balance and neuronal injury. II. A conditioning lesion paradigm.

The PC12 rat pheochromocytoma cell line is a nerve growth factor (NGF) responsive line that is protected by NGF from the toxic effects of hydrogen peroxide induced peroxidation. In part, NGF protection of PC12 cells acts through a shift in oxidant-antioxidant metabolism by the enhancement of catalase activity. When PC12 cells are used in a conditioning lesion paradigm to study the effects of an initial sublethal peroxidative insult on subsequent responses to injury, a low dose conditioning lesion protects even in the absence of NGF. The magnitude of the protective effect exerted by the conditioning lesion, however, is augmented in the presence of NGF, since a significant cytoprotective effect is observed over a wider range of H2O2 concentrations. Neuronal injury due to treatment with a high dose of H2O2 (5 mM) has a cytotoxic effect that cannot be prevented by NGF treatment and is, in itself, not conditioning in nature. This in vitro model system lends itself to the development of explanations regarding the salutory effects of conditioning lesions at the molecular level.

Animals↗

PubMed1990

Measuring visual acuity in children using preferential looking and sine wave cards.

Preferential looking using square waves is commonly used to measure visual acuity of infants. Since sine-wave gratings have the advantage of presenting only a single spatial frequency, we completed a study to develop and validate a set of acuity cards using sine waves. The subjects were 83 children (mean age = 41.5 months, range = 3 to 69 months). The sine-wave cards were compared with Teller cards. Identical visual acuity was determined in 83% of the cases. Wilcoxon non-parametric analysis provided no evidence to reject the null hypothesis of equal visual acuities between the two methods. We conclude that sine-wave cards may be used to measure the preferential looking acuity of children.

Child↗

PubMedDate not supplied

Nerve growth factor and neuronal cell death.

The regulation of neuronal cell death by the neuronotrophic factor, nerve growth factor (NGF), has been described during neural development and following injury to the nervous system. Also, reduced NGF activity has been reported for the aged NGF-responsive neurons of the sympathetic nervous system and cholinergic regions of the central nervous system (CNS) in aged rodents and man. Although there is some knowledge of the molecular structure of the NGF and its receptor, less is known as to the mechanism of action of NGF. Here, a possible role for NGF in the regulation of oxidant--antioxidant balance is discussed as part of a molecular explanation for the known effects of NGF on neuronal survival during development, after injury, and in the aged CNS.

Amino Acid Sequence↗

PubMedDate not supplied

Aging and feature search: the effect of search area.

The preattentive system involves the rapid parallel processing of visual information in the visual scene so that attention can be directed to meaningful objects and locations in the environment. This study used the feature search methodology to examine whether there are aging-related deficits in parallel-processing capabilities when older adults are required to visually search a large area of the visual field. Like young subjects, older subjects displayed flat, near-zero slopes for the Reaction Time x Set Size function when searching over a broad area (30 degrees radius) of the visual field, implying parallel processing of the visual display. These same older subjects exhibited impairment in another task, also dependent on parallel processing, performed over the same broad field area; this task, called the useful field of view test, has more complex task demands. Results imply that aging-related breakdowns of parallel processing over a large visual field area are not likely to emerge when required responses are simple, there is only one task to perform, and there is no limitation on visual inspection time.

Adult↗

PubMedDate not supplied

Aging and spatial localization during feature search.

BACKGROUND: Previous studies indicate that older adults, like young adults, can efficiently search for a briefly presented visual target defined by a single salient feature presented amidst background distractors. However, little is known about older adults' ability to identify the spatial location of targets during this aspect of preattentive processing. OBJECTIVE: This study examined the extent to which older adults exhibit localization problems during feature search for a target with high conspicuity. Their performance was compared to that of younger adults. METHODS: Twenty older adults (mean age 70 years, 8 men and 12 women) and 20 younger adults (mean age 25 years, 6 men and 14 women) with good central and peripheral vision were tested. Subjects were asked to indicate via a computerized touch-screen the location of a briefly presented (80 ms) target presented amidst distracting stimuli (set size 8, 16, or 32). Targets were presented at either 10 degrees, 20 degrees, or 30 degrees eccentricity. The dependent measures were percent correct localization and, for trials in which there were errors, the spatial magnitude of the error. RESULT: Compared to young adults, older adults committed more localization errors during feature search, a problem which was accentuated with increasing target eccentricity. In addition, older adults' mislocalizations deviated from the correct location by greater distances. CONCLUSIONS: Older adults have spatial localization problems in preattentive processing during feature search, which could be detrimental to the guidance and deployment of visual attention.

Adult↗