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Biomedical subjects

L Lim

Publications and source records attributed to L Lim.

At least 199 records · Page 11Linked to original sources
PubMed1982

Type A and type B monoamine oxidase activities in rat brain and liver mitochondria: a comparison of their properties using the non-ionic detergent Triton X-100.

1. The effects of the non-ionic detergent Triton X-100 on the heterogeneity of monoamine oxidase activities were studied and compared in synaptic (fractions SM and SM2) and non-synaptic (fraction M) brain mitochondria and liver mitochondria. 2. Triton X-100 inhibited type A and type B monoamine oxidase activities in all four mitochondrial fractions in a concentration-dependent manner. Liver mitochondrial enzymatic activities were much more sensitive to this inhibition than those of brain mitochondria. The activities in the SM fraction of synaptic brain mitochondria were the least susceptible. 3. In all four mitochondrial fractions, type A activities were more sensitive to inhibition than type B activities. 4. These results suggest that the membrane micro-environment around the enzyme molecules in situ may be important in the functional expression of the activity of the enzyme.

Animals↗
PubMed1982

The effects of chronic manganese feeding on the activity of monoamine oxidase in various organs of the developing rat.

1. Chronic manganese feeding of rat with doses as high as 10 mg/ml in drinking water had no effect on body weight increases during postnatal development. The organ weight increases in brain, liver, heart and kidney also remained unaffected, but spleen weight was consistently lower than in the age-matched controls after Mn-feeding, being more marked at the higher doses. An increase in the Mn concentration to 20 mg/ml led to drastic body weight losses not unlike that seen in malnutrition. 2. There were differential developmental changes in monoamine oxidase (MAO) with respect to tissue type and substrate used. Manganese feeding did not affect the developmental patterns of MAO in brain, heart and kidney. However, hepatic MAO activities towards 5-HT and BzNH2 were found to increase after 10--15 days of postnatal life. 3. In contrast, the activity in the spleen towards 5-HT was lower in the high Mn-treated group in the first few days post-partum.

Aging↗
PubMed1982

Effects of Cd2+, Mn2+, and Al3+ on rat brain synaptosomal uptake of noradrenaline and serotonin.

Cd2+, Mn2+, and Al3+ inhibited synaptosomal amine uptake in a concentration-dependent and time-dependent manner. In the absence of Ca2+, the rank order of inhibition of noradrenaline uptake was: Cd2+ (IC50 = 250 microM) greater than Al3+ (IC50 = 430 microM) greater than Mn2+ (IC50 = 1.50 mM), the IC50 being the concentration of metal ions that gave rise to 50% inhibition of uptake. In the presence of 1 mM Ca2+, the rank order of inhibition of uptake was: Al3+ (IC50 = 330 microM) greater than Cd2+ (IC50 = 540 microM) greater than (IC50 = 1.5 mM). The rank order of inhibition of serotonin uptake without Ca2+ was: Al3+ (IC50 = 370 microM) greater than Cd2+ (IC50 = 610 microM) greater than Mn2+ (IC50 = 3.4 mM) and the rank order in the presence of 1 mM Ca2+ was: Al3+ (IC50 = 290 microM) greater than Cd2+ (IC50 = 1.5 mM) greater than Mn2+ (IC50 = 4.0 mM). Ca2+, at 1 mM, definitely antagonized the inhibitory actions of Cd2+ on noradrenaline and serotonin uptake. Al3+ stimulated noradrenaline uptake at concentrations around 20-250 microM but inhibited this uptake at concentrations exceeding 300 microM in a dose-related fashion. Ca2+, at 1 mM, enhanced both the stimulatory and inhibitory effects of Al3+. Ca2+ also enhanced the inhibitory actions of Al3+ on serotonin uptake. These results, in conjunction with those we have previously published, suggest that Cd2+, Mn2+, and Al3+ exert differential and selective effects on the structure and function of synaptosomal membranes.

Aluminum↗
PubMed1982

The ontogeny of acetylcholinesterase activities in rat brain regions and the effect of chronic treatment with manganese chloride.

Acetylcholinesterase activities were determined in the rat cerebral cortex, striatum, midbrain, pons and medulla, hypothalamus, and cerebellum at 5, 12, 20, 30, and 60 days after birth. The ontogeny of the enzyme differed in the various regions, occurring earlier in the more caudal regions, except in the cerebellum where there was no increase. Chronic manganese treatment from conception did not influence the developmental profile of this cholinergic marker.

Acetylcholinesterase↗
PubMed1982

The effects of chronic manganese chloride treatment expressed as age-dependent, transient changes in rat brain synaptosomal uptake of amines.

As a result of chronic manganese treatment of rats from conception onwards, a decrease was observed in the uptake of dopamine, but not of noradrenaline or serotonin, by synaptosomes isolated from hypothalamus, striatum, and midbrain and in choline uptake by hypothalamic synaptosomes obtained from 70-90-day-old animals. In 100-120-day-old manganese-treated rats the only difference observed was increased choline uptake by striatal synaptosomes. All comparisons were with age-matched controls. These results, which are consistent with views of a dopaminergic and cholinergic involvement in manganese encephalopathy, point out that changes in these systems are observable only at specific times during manganese intoxication.

Aging↗
PubMed1982

Activities of the mitochondrial NAD-linked isocitric dehydrogenase in different regions of the rat brain: changes in ageing and the effect of chronic manganese chloride administration.

The specific activities of NAD-linked isocitric dehydrogenase were determined in hypothalamus, cerebellum, pons and medulla, striatum, midbrain, and cerebral cortex (which included the hippocampus) of the female Wistar rat. In ageing the specific activities of this enzyme were decreased in all regions. Chronic treatment with manganese chloride from conception onwards for a period of over 2 years appeared to counteract there decreases during ageing. However, manganese had no apparent effect on the specific activities of this enzyme in different brain regions of 2-month-old animals.

Aging↗
PubMed1981

The nuclear oestrogen receptor in the female rat. Effects of oestradiol administration during the oestrous cycle on the uterus and contrasting effects of progesterone on the uterus and hypothalamus.

Oestradiol administration to immature or ovariectomized rats has been reported to increase the uterine content of long-term nuclear oestrogen receptors. However, in the intact adult female rat, oestradiol administration did not increase the concentration of long-term nuclear oestrogen receptors at all phases of the oestrous cycle. Progesterone administration to rats in late dioestrus did not affect the concentration of uterine nuclear oestrogen receptors 24 h later, although it did prevent the normal cyclic increase at pro-oestrus in the concentration of hypothalamic nuclear oestrogen receptors. Our results therefore show that in the intact adult rat, factors other than the concentration of progesterone or oestradiol determine the nuclear concentration of oestrogen receptors in the uterus. They also demonstrate differences between neural and non-neural tissues in the regulation of oestrogen-receptor interactions.

Animals↗
PubMed1981

The relationship of the oestrogen and progestin receptors in the abnormal uterus of the adult anovulatory rat. Effects of neonatal treatment with testosterone propionate or clomiphene citrate.

The neonatal administration of testosterone propionate to Wistar rats resulted in anovulatory adults in persistent vaginal oestrus. Clomiphene citrate had a similar effect. In both groups of adults, hyperplasia of the uterine epithelium and occasional metaplasia was observed. The uterine nuclear and cytosol oestrogen and progestin receptors of these anovulatory rats were found to have affinities for their respective ligands similar to those of normal females. The nuclear oestrogen receptor comprised occupied and unoccupied components, as in normal females. The content of the nuclear oestrogen receptor was comparable with that of females in the late dioestrous or pro-oestrous phase. This content was higher in the clomiphene-treated group. Despite the relatively high nuclear oestrogen receptor content the content of progestin receptors, a putative index of the oestrogenic response, was lower in the treated rats than in normal adult females throughout the cycle. Administration of oestradiol to both treatment groups resulted in depletion of cytosol oestrogen receptor content 1 h later, which, however, was not reflected by an increase in the content of nuclear oestrogen receptors. There was no measurable increase in progesterone receptor content in treated rats after daily administration of oestrogen (5 microgram/rat) for 3 days. These changes in sex-hormone-receptor interactions involving an impairment of the normal oestrogenic response may be associated with the abnormal differentiation of the uterus in these sterile, anovulatory animals.

Animals↗
PubMed1981

Chromatin organization in the rat hypothalamus during early development.

The organization of chromatin in neuronal and glial nuclei isolated from different brain regions of rats during development was studied by digestion of nuclei with micrococcal nuclease. A short chromatin repeat length (approx. 176 base-pairs compared with that of glial nuclei from foetal cerebral cortex (approx. 200 base-pairs) was present in hypothalamic neurons throughout the ages studied, which was similar to the repeat length of cortical neurons from 7- and 25-day-old animals (approx. 174 base-pairs). Whereas in cortical neurons the chromatin repeat length shortened from approx. 200 base-pairs in the foetus to approx. 174 base-pairs in the first postnatal week, the short chromatin repeat length of hypothalamic neurons was already present 2 days before birth, indicating that hypothalamic neurons differentiate earlier than cortical neurons during brain development.

Animals↗
PubMed1981

Developmental changes in the composition of polyadenylated RNA isolated from free and membrane-bound polyribosomes of the rat forebrain, analysed by translation in vitro.

Free and membrane-bound polyribosomes were isolated from the rat forebrain during its development. Polyadenylated RNA [poly(A)+ RNA] was isolated from both fractions, by using oligo(dT)-cellulose chromatography, and its composition studied by translating the poly(A)+ RNA in vitro in reticulocyte lysates. Electrophoretic analysis of the translation products showed that both free and membrane-bound polyribosomal poly(A)+ RNA gave many common components, but that there were also distinct differences in the protein composition of the products of the two fractions. Several proteins, of mol.wts. 39 000, 37 000, 31 000, 27 000 and 17 000, appeared to be products predominantly of free polyribosomal poly(A)+ RNA, whereas others, of mol.wt. 47 000, 33 000, 24 000 and 21 000 were specific to the membrane-bound polyribosomal poly(A)+ RNA fraction. More developmental changes were observed in the translational products of the membrane-bound poly(A)+ RNA fraction. Proteins of mol.wts. 33 000 and 21 000, which were predominant components of the translational products of this fraction when isolated from 10-day and older rats, were not present in translational products derived from preparations isolated from 3-day-old rats. The developmental appearance of these proteins as translational products of the membrane-bound poly(A)+ RNA suggests the appearance of new mRNA species. These transcriptional changes are discussed in relation to processes involved in brain differentiation, including myelination.

Animals↗
PubMed1981

The unoccupied nuclear oestradiol receptor in the rat uterus and hypothalamus during the oestrous cycle.

The nuclear oestrogen receptor population in the rat uterus contained an unoccupied receptor component that bound oestradiol with the high affinity (Kd congruent to 0.5 nM) characteristic of oestrogen receptors. This unoccupied receptor was present at all phases of the oestrous cycle. Its content changed in parallel with that of the total nuclear receptor during the cycle. Oestradiol administration to the immature rat resulted in increases in the uterine content of long-term nuclear receptors (i.e., those still present 8 h after administration); these increases were due to occupied oestrogen receptors, since the content of unoccupied receptor was unchanged. Our previous experiments [White & Lim (1980) Biochem. J. 190, 833-837] have shown in contrast, that oestradiol administration results in an increase in the content of unoccupied nuclear receptor in the hypothalamus. However, as in the uterus, similar cyclic changes in the content of unoccupied nuclear receptor occurred in parallel with those of the total nuclear receptor population in the hypothalamus. Differences and similarities between the unoccupied nuclear receptor of the uterus and hypothalamus are briefly discussed.

Animals↗
PubMed1981

Selective inhibition of L-glutamate and gammaaminobutyrate transport in nerve ending particles by aluminium, manganese, and cadmium chloride.

AlCl3, MnCl2, and CdCl2 inhibited the rates of accumulation of [14C] L-glutamate and [3H] gammaaminobutyrate (GABA) in purified rat forebrain nerve-ending particles in a dose-dependent fashion. The concentrations that would give 50% inhibition (IC50) of GABA transport were 316 muM, 7.4 mM, and 1.4 mM, respectively. Ca2+ (1 mM) enhanced the inhibitory effect of Al3+ (IC50 decreased to 149 muM) but antagonized that of Mn2+ (IC50 = 10 mM) and Cd2+ (IC50 = 2.1 mM). For glutamate transport 1 mM Ca2+ changed the IC50 values from 299 to 224 micron for Al3+, 7.1 to 10 mM for Mn2+, and 2 to 3 mM for Cd2+. In contrast, the rates of accumulation of [14C] 2-deoxy-glucose and [3H] L-phenylalanine were mostly unaffected by these metal ions. The results indicate that Al3+, Mn2+, and Cd2+ exerted selective and differential effects on the transport systems of neurotransmitter substances in the synaptosomal membrane.

Aluminum↗
PubMed1981

Brain regional distribution of glutamic acid decarboxylase, choline acetyltransferase, and acetylcholinesterase in the rat: effects of chronic manganese chloride administration after two years.

Rats were treated chronically with manganese chloride from conception onward for a period of over 2 years in order to study the effects of manganese and aging on the activities of glutamic acid decarboxylase (GAD), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) in hypothalamus, cerebellum, pons and medulla, striatum, midbrain, and cerebral cortex (which included the hippocampus). Manganese-treated 2-month-old and 24- to 28-month-old rats and age-matched controls were studied. In control rats during aging the activities of GAD decreased in hypothalamus (19%), pons and medulla (28%), and midbrain (22%) whereas the activities of AChE decreased in all regions (20-48%), particularly in the striatum (44-48%). Changes in ChAT activities in aging were observed only in one region-a decrease (23%) in the striatum. Life-long treatment with manganese appeared to abolish partially the decreases in aging in AChE activities in hypothalamus, cerebellum and striatum, and striatal ChAT activity. Manganese treatment also seemed to abolish the age-related decreases GAD activities, since GAD activities in various brain regions of manganese-treated senescent rats were not significantly different from those of control young rats. These results are discussed in relation to other metabolic changes associated with aging and manganese toxicity.

Acetylcholinesterase↗