Uptake and toxicity of toxaphene to cell cultures derived from goldfish (Carassius auratus).
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Animals↗
Biomedical subjects
T B Shea
Publications and source records attributed to T B Shea.
Chronic exposure of goldfish-derived cell cultures to toxaphene alters the replication of Goldfish Virus-2.
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Animals↗
Unoccupied and occupied estrogen receptors in myometrial cytosol and nuclei from nonpregnant and pregnant women.
Exchange assays have been developed and used to measure the total concentration of estrogen receptor sites (unoccupied and occupied with endogenous hormone) in the cytosol and nuclei of human myometrium during the menstrual cycle and in pregnancy at term, before and during labor. A major fraction of the nuclear receptors appear to be unoccupied (not complexed with estrogen). These sites were detected in both crude and highly purified myometrial nuclei, indicating that they are located in the nucleus and do not represent a cytoplasmic or other cellular contaminant. The distribution of estrogen receptors between the cytosol and the nucleus varied in pregnant and nonpregnant patients. In pregnant patients, the receptor was detected only in the nucleus, while in nonpregnant patients most of the receptor was found in the cytosol. The levels of total receptor were considerably lower (5 times) in pregnancy at term than during the menstrual cycle. No significant differences in cytosol receptor levels or in unoccupied nuclear receptor levels were observed between the proliferative and secretory phases of the cycle. However, the levels of occupied nuclear receptors were significantly higher in the proliferative than in the secretory phase. The levels of total and occupied nuclear receptors in pregnancy at term were similar to those found during the proliferative phase and appeared to decrease somewhat during labor, although the differences were not statistically significant.
Cell Nucleus↗
Electron microscopy of the morphogenesis of Bacillus subtilis bacteriophage SP3.
The capsid of Bacillus subtilis bacteriophage SP3 is assembled via a prohead intermediate which subsequently encapsulates DNA and attaches a tail. The prohead contains a ring-like core structure. The spokes which extend from the core to the inner prohead surface are thought to form a scaffold for the polymerization of the prohead. Ninety percent of the proheads are assembled prior to the onset of DNA encapsulation. The first mature phage particles are observed at 45 min after infection; titres of intracellular phage demonstrate their infectivity. The core is visible in phage ghosts.
Bacillus subtilis↗
Aluminum inhibits neurofilament assembly, cytoskeletal incorporation, and axonal transport. Dynamic nature of aluminum-induced perikaryal neurofilament accumulations as revealed by subunit turnover.
The mechanism by which aluminum induces formation of perikaryal neurofilament (NF) inclusions remains unclear. Aluminum treatment inhibits: 1. The incorporation of newly synthesized NF subunits into Triton-insoluble cytoskeleton of axonal neurites; 2. Their degradation and dephosphorylation; 3. Their translocation into axonal neurites. It also fosters the accumulation of phosphorylated NFs within perikarya. In the present study, we addressed the relationship among these effects. Aluminum reduced the assembly of newly synthesized NF subunits into NFs. During examination of those subunits that did assemble in the presence of aluminum, it was revealed that aluminum also interfered with transport of newly assembled NFs into axonal neurites. Similarly, a delay in axonal transport of microinjected biotinylated NF-H was observed in aluminum-treated cells. Aluminum also inhibited the incorporation of newly synthesized and microinjected subunits into the Triton-insoluble cytoskeleton within both perikarya and neurites. Once incorporated into Triton-insoluble cytoskeletons, however, biotinylated subunits were retained within perikarya of aluminum-treated cells to a greater extent than within untreated cells. Notably, these subunits were depleted in the presence and absence of aluminum within 48 h, despite the persistence of the aluminum-induced perikaryal accumulation itself, suggesting that individual NF subunits undergo turnover even within aluminum-induced perikaryal accumulations. These findings demonstrate that aluminum interferes with multiple aspects of neurofilament dynamics and furthermore leaves open the possibility that aluminum-induced perikaryal NF whorls may not represent permanent structures, but rather may require continued recruitment of cytoskeletal constituents.
Aluminum↗
Calcium modulates aluminum neurotoxicity and interaction with neurofilaments.
We examined the influence of calcium on neurotoxicity of AlCl3 and Al-lactate toward differentiated NB2a/d1 cells. Apart from induction of perikaryal neurofibrillary inclusions, AlCl3 at 1 mM induced no obvious additional signs of toxicity when added to culture medium in the presence of the normal medium CaCl2 content of 1.8 mM, nor when extracellular calcium was decreased by the addition to the medium of 0.9 mM EDTA. Increasing the extracellular CaCl2 concentration by fivefold was only marginally toxic, but in the presence of AlCl3, reduced viable cell numbers by well over 50% as compared to control cultures, and by approximately 50% vs fivefold CaCl2 alone. A twofold increase in extracellular CaCl2 did not increase the percentage of cells exhibiting Bielschowsky-positive perikarya, but induced a near doubling in the percentage of cells exhibiting accumulations in the presence of 1 mM Al-lactate. AlCl3 (1 mM) retards the electrophoretic migration of NF subunits on SDS-gels. This effect was eliminated by withholding CaCl2 from the incubation mixture and including 5 mM EDTA during incubation of cytoskeletons with AlCl3. The presence of CaCl2 alone did not alter NF migration. These findings underscore the possibility that multiple factors, including those that compromise general neuronal homeostasis, may contribute to neurofibrillary pathology.
Aluminum↗
Relative susceptibility of cytoskeleton-associated and soluble neurofilament subunits to aluminum exposure in intact cells. A possible mechanism for reduction of neurofilament axonal transport during aluminum neurotoxicity.
Previous studies have demonstrated the appearance of phosphorylated neurofilament (NF) subunits within perikaryal cytoskeletons following aluminum exposure. In order to examine the mechanisms leading to this altered distribution of NF subunits, we carried out biochemical analyses of NF subunits in Triton-insoluble and -soluble fractions derived from aluminum-treated NB2a/d1 cells. In addition to increases in the Triton-insoluble cytoskeleton, increases in all three NF subunits were also detected within the Triton-soluble fraction of aluminum-treated cells. To address the nature of this increase in Triton-soluble subunits, aluminum-treated and untreated cultures were harvested in the absence of Triton and fractionated by established procedures to yield fractions greatly enriched for perikarya and neurites, respectively. Each of these subcellular fractions was then subjected to further homogenization in the presence of 1% Triton and centrifugation to yield Triton-insoluble cytoskeletons and Triton-soluble material derived from perikarya and axonal neurites, respectively. Resulting Triton-soluble fractions were "clarified" by high-speed centrifugation to eliminate oligomeric assemblies or soluble neurofilaments. Immunoblot analysis demonstrated quantitative recovery of the aluminum-induced increase in Triton-soluble NF subunits in the perikaryal fraction. Additional aluminum-treated and untreated cultures were pulse-chase radiolabeled with [35S]methionine and fractionated into Triton-insoluble and soluble fractions from isolated perikarya and axonal neurites. Autoradiographic analysis of immunoprecipitated NF subunits revealed that aluminum treatment delayed the translocation of newly synthesized subunits into neurites and resulted in the accumulation of radiolabeled subunits within the Triton-soluble fraction of perikarya. These findings suggest that aluminum may exert a relatively greater effect on NF subunits that have not yet undergone axonal transport and/or incorporation into Triton-insoluble structures vs those that have already deposited into axons. This possibility was supported by the observation that a higher concentration of aluminum was required to alter the electrophoretic migration of in vitro reassembled neurofilaments vs that required for unassembled NF subunits. These findings provide possible mechanisms for the accumulation of NF subunits in perikarya during aluminum intoxication.
Aluminum↗
Microtubule motors, phosphorylation and axonal transport of neurofilaments.
The recent demonstration that the axonal transport motors kinesin and dynein participate in axonal transport of neurofilaments (NFs), and that the association of NFs with these motors is regulated by phosphorylation provides new insight into several aspects of axonal transport and NF biology. This review juxtaposes older and more recent findings on NF dynamics, and speculates on the organization of axonal NFs as suggested by real-time analyses of NF transport.
Animals↗
S-adenosyl methionine: A connection between nutritional and genetic risk factors for neurodegeneration in Alzheimer's disease.
Clinical manifestation of Alzheimer's disease may depend upon interaction among its risk factors. Apolipoprotein E-deficient mice undergo oxidative damage and cognitive impairment when deprived of folate. We demonstrate herein that these mice were depleted in the methyl donor S-adenosyl methionine (SAM), which inhibited glutathione S-transferase, since this enzyme requires methylation of oxidative species prior to glutathione-dependent reduction. Dietary supplementation with SAM alleviated neuropathology. Since SAM deficiency promotes presenilin-1 overexpression, which increases gamma-secretase expression and Abeta generation, these findings directly link nutritional deficiency and genetic risk factors, and support supplementation with SAM for Alzheimer's therapy.
Adenosine↗