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991.
Oxidative damage is associated with Alzheimer's disease and mild cognitive impairment, but its relationship to the development of neuropathological lesions involving accumulation of amyloid-beta (Abeta) peptides and hyperphosphorylated tau protein remains poorly understood. We show that inducing oxidative stress in primary chick brain neurons by exposure to sublethal doses of H(2)O(2 )increases levels of total secreted endogenous Abeta by 2.4-fold after 20 h. This occurs in the absence of changes to intracellular amyloid precursor protein or tau protein levels, while heat-shock protein 90 is elevated 2.5-fold. These results are consistent with the hypothesis that aging-associated oxidative stress contributes to increasing Abeta generation and up-regulation of molecular chaperones in Alzheimer's disease. 相似文献
992.
Tripathi S Somashekar BS Mahdi AA Gupta A Mahdi F Hasan M Roy R Khetrapal CL 《Journal of biochemical and molecular toxicology》2008,22(2):119-127
The toxic effects of Al(3+) have been studied in 90-days AlCl(3) orally treated male albino rats (n = 7) using (1)H NMR spectroscopy-based metabolic profile of rat serum and urine, serum enzyme tests, behavioral impairment, and histopathology of kidney and liver. Metabolic profile of 90-days Al(3+)-treated rat sera showed significantly elevated levels of alanine, glutamine, beta-hydroxy-butyrate, and acetoacetate and significantly decreased level of acetone when compared with that of control rats. However, metabolic profile of 90-days Al(3+)-treated rat urine showed significantly decreased levels of citrate, creatinine, allantoin, trans-aconitate, and succinate and significantly increased level of acetate when compared to control rats. The overall perturbations observed in the metabolic profile of serum and urine demonstrate the impairment in the tricarboxylic acid cycle, liver and kidney metabolism, which was further reinstated by clinical chemistry and histopathological observations. Moreover, "in vivo" behavioral impairment has also been observed as the indication of aluminum neurotoxicity. 相似文献
993.
The Na+-independent binding of [3H]-alanine to rat brain stem plus spinal cord was reinvestigated, in order to study in more detail the characteristics of previously described -alanine binding processes. Binding was absent when amino acid-free postnuclear supernatants or crude synaptic membranes were used. Experiments performed with several other Na+-free preparations showed a sole binding component, irrespective of the preparation used. Biochemical characterization of this Na+-independent binding, using frozen/thawed/washed synaptosomal-mitochodrial fractions, showed that binding reached a plateau between 7 min and 13 min, increasing thereafter. Binding was linear with fraction protein over a range of 200–415 g/ml incubation medium. Binding was completely inhibited by glycine, alanine, -aminobutyric acid, -aminoisobutyric acid, hypotaurine and strychnine, and to a lesser extent by 2,2-dimethyl--alanine, brucine and gelsemine. It was insensitive to taurine, -aminobutyric acid (GABA), 2-guanidinoethanesulfonic acid (GES), carnosine, and bicuculline methiodide. Binding was reversible, saturable (K
D 20 M), and heat sensitive. 相似文献
994.
995.
Longer lifespan in male mice treated with a weakly estrogenic agonist,an antioxidant,an α‐glucosidase inhibitor or a Nrf2‐inducer 下载免费PDF全文
Adam Antebi Clinton M. Astle Molly Bogue Martin S. Denzel Elizabeth Fernandez Kevin Flurkey Karyn L. Hamilton Dudley W. Lamming Martin A. Javors João Pedro de Magalhães Paul Anthony Martinez Joe M. McCord Benjamin F. Miller Michael Müller James F. Nelson Juliet Ndukum G. Ed. Rainger Arlan Richardson David M. Sabatini Adam B. Salmon James W. Simpkins Wilma T. Steegenga Nancy L. Nadon David E. Harrison 《Aging cell》2016,15(5):872-884
The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin – the latter with and without rapamycin, and two drugs previously examined: 17‐α‐estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17‐α‐estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male‐specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α‐glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies. 相似文献
996.
997.
Quantification of ventricular β2‐adrenoceptor density and ligand binding affinity in wild sockeye salmon Oncorhynchus nerka smolts using a novel modification to the tritiated ligand technique 下载免费PDF全文
A new, image‐based, tritiated ligand technique for measuring cardiac β2‐adrenoceptor (β2‐AR) binding characteristics was developed and validated with adult rainbow trout Oncorhynchus mykiss hearts so that the tissue limitation of traditional receptor binding techniques could be overcome and measurements could be made in hearts nearly 14‐times smaller than previously used. The myocardial cell‐surface (functional) β2‐AR density of O. nerka smolts sampled at the headwaters of the Chilko River was 54·2 fmol mg protein?1 and about half of that previously found in return migrating adults of the same population, but still more than twice that of adult hatchery O. mykiss (21·1 fmol mg protein?1). This technique now opens the possibility of investigating cardiac receptor density in a much wider range of fish species and life stages. 相似文献
998.
We examined the effects of the conversion of tropical forest to pasture on soil organic matter (SOM) origin and quality along
a chronosequence of sites, including a primary forest and six pastures. Bulk soil samples received a physical size-fractionation
treatment to assess the contribution of each compartment to total SOM pool. Besides a general increase in total C and N stocks
along the chronosequence, we observed a reduction of the relative contribution of the coarser fractions to total soil C content,
and an increased concentration in the finer fractions. The origin of the C in each size fraction was established from measurements
of13C abundance. After 80 years about 93% of the C in the least humified fraction of the top 10 cm of soil was of pasture origin,
while in the most humified it was 82%. Chemical analyses indicated that the fine silt and coarse clay fractions contained
the most refractory carbon. 相似文献
999.
1000.
Circular RNAs (circRNAs) has been shown to play an important role in the progression of various cancers. However, the function and underlying mechanisms of circRNAs affecting chemotherapy resistance in esophageal squamous cell carcinoma (ESCC) remain largely unknown. In this study, we used gefitinib-resistant (GR) ESCC cells to investigate the function of circPSMC3 and clarify the underlying mechanism in chemotherapy resistance in ESCC. The results suggested that circPSMC3 expression was downregulated, but miR-10a-5p was upregulated in ESCC tissues and cells, as well as in GR ESCC cells. CircPSMC3 overexpression increased the sensitivity of ESCC cells to gefitinib, as indicated by reduced half maximal inhibitory concentration value, increased apoptosis rate and cleaved caspase-3 protein expression. CircPSMC3 directly interacted with miR-10a-5p and inhibited the expression of miR-10a-5p. Phosphatase and tensin homolog (PTEN) was a direct target of miR-10a-5p and circPSMC3 promoted PTEN expression via decreasing miR-10a-5p level. Moreover, the effect of circPSMC3 on resistance of GR ESCC cells to gefitinib was remarkably reduced by restoration of miR-10a-5p and downregultion of PTEN. Taken together, these observations suggested that upregulation of circPSMC3 overcame resistance of GR ESCC cells to gefitinib by modulating the miR-10a-5p/PTEN axis, which provide a new therapeutic strategy for overcoming gefitinib resistance in ESCC. 相似文献