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991.
992.
Endomannosidase processes oligosaccharides of α1-antitrypsin and its naturally occurring genetic variants in the Golgi apparatus 总被引:3,自引:0,他引:3
Torossi T Fan JY Sauter-Etter K Roth J Ziak M 《Cellular and molecular life sciences : CMLS》2006,63(16):1923-1932
Endomannosidase provides an alternate glucose-trimming pathway in the Golgi apparatus. However, it is unknown if the action
of endomannosidase is dependent on the conformation of the substrate. We have investigated the processing by endomannosidase
of the α1-antitrypsin oligosaccharides and its disease-causing misfolded Z and Hong Kong variants. Oligosaccharides of wild-type
and misfolded α1-antitrypsin expressed in castanospermine-treated hepatocytes or glucosidase II-deficient Phar 2.7 cells were
selectively processed by endomannosidase and subsequently converted to complex type oligosaccharides as indicated by Endo
H resistance and PNGase F sensitivity. Overexpression of endomannosidase in castanospermine-treated hepatocytes resulted in
processing of all oligosaccharides of wild-type and variants of α1-antitrypsin. Thus, endomannosidase does not discriminate
the folding state of the substrate and provides a back-up mechanism for completion of N-glycosylation of endoplasmic reticulum-escaped glucosylated glycoproteins. For exported misfolded glycoproteins, this would
provide a pathway for the formation of mature oligosaccharides important for their proper trafficking and correct functioning.
Received 18 April 2006; received after revision 12 June 2006; accepted 15 June 2006 相似文献
993.
Endocannabinoids and β-amyloid-induced neurotoxicity in vivo: effect of pharmacological elevation of endocannabinoid levels 总被引:3,自引:0,他引:3
van der Stelt M Mazzola C Esposito G Matias I Petrosino S De Filippis D Micale V Steardo L Drago F Iuvone T Di Marzo V 《Cellular and molecular life sciences : CMLS》2006,63(12):1410-1424
We investigated the involvement of endocannabinoids in the control of neuronal damage and memory retention loss in rodents
treated with the β-amyloid peptide (1–42) (BAP). Twelve days after stereotaxic injection of BAP into the rat cortex, and concomitant
with the appearance in the hippocampus of markers of neuronal damage, 2-arachidonoyl glycerol, but not anandamide, levels
were enhanced in the hippocampus. VDM-11 (5 mg/kg, i.p.), an inhibitor of endocannabinoid cellular reuptake, significantly
enhanced rat hippocampal and mouse brain endocannabinoid levels when administered sub-chronically starting either 3 or 7 days
after BAP injection and until the 12–14th day. VDM-11 concomitantly reversed hippocampal damage in rats, and loss of memory
retention in the passive avoidance test in mice, but only when administered from the 3rd day after BAP injection. We suggest
that early, as opposed to late, pharmacological enhancement of brain endocannabinoid levels might protect against β-amyloid
neurotoxicity and its consequences.
Received 26 January 2006; received after revision 24 March 2006; accepted 12 April 2006 相似文献
994.
GenePattern 2.0 总被引:1,自引:0,他引:1
995.
Mitochondria and calpains mediate caspase-dependent apoptosis induced by doxycycline in HeLa cells 总被引:2,自引:0,他引:2
Doxycycline (Dc) has been demonstrated to inhibit cell growth and induce apoptosis in tumor cells, although its mechanism
of action is not fully understood. The present study demonstrates that apoptosis can be induced in HeLa cells. Western blot
data demonstrated that cytochrome c (Cyt c), Smac (the second mitochondria-derived activator of caspase), calpain I, caspase-9,
−3 and −8 were involved in the apoptotic process, while the pan caspase inhibitor zVAD-fmk almost completely inhibited Dc-induced
apoptosis. We further demonstrated that the release of mitochondrial proteins and the activation of calpains occurred upstream
of the caspase cascade, in which caspase-9 was activated in response to the release of Cyt c, that caspase-8 activation was
caspase and calpain dependent, and that caspase-3 was activated mainly by caspase-8 and −9. Caspase-8 played important roles
in the activation of caspase-3 and induction of apoptosis, whereas the role of the caspase-9 was limited.
Received 26 November 2005; received after revision 14 February 2006; accepted 1 March 2006 相似文献
996.
Molecular targets of glioma invasion 总被引:9,自引:1,他引:8
Nakada M Nakada S Demuth T Tran NL Hoelzinger DB Berens ME 《Cellular and molecular life sciences : CMLS》2007,64(4):458-478
Glioblastoma multiforme is the most common and lethal primary malignant brain tumor. Although considerable progress has been
made in technical proficiencies of surgical and radiation treatment for brain tumor patients, the impact of these advances
on clinical outcome has been disappointing, with median survival time not exceeding 15 months. Over the last 30 years, no
significant increase in survival of patients suffering from this disease has been achieved. A fundamental source of the management
challenge presented in glioma patients is the insidious propensity of tumor invasion into distant brain tissue. Invasive tumor
cells escape surgical removal and geographically dodge lethal radiation exposure and chemotherapy. Recent improved understanding
of biochemical and molecular determinants of glioma cell invasion provide valuable insight into the underlying biological
features of the disease, as well as illuminating possible new therapeutic targets. These findings are moving forward to translational
research and clinical trials as novel antiglioma therapies.
Received 25 July 2006; received after revision 27 October 2006; accepted 22 November 2006 相似文献
997.
Molecular mechanisms of nitrosative stress-mediated protein misfolding in neurodegenerative diseases
Nitrosative and oxidative stress, associated with the generation of excessive reactive oxygen or nitrogen species, are thought
to contribute to neurodegenerative disorders. Many such diseases are characterized by conformational changes in proteins that
result in their misfolding and aggregation. Accumulating evidence implies that at least two pathways affect protein folding:
the ubiquitin-proteasome system (UPS) and molecular chaperones. Normal protein degradation by the UPS can prevent accumulation
of aberrantly folded proteins. Molecular chaperones – such as protein-disulfide isomerase, glucose-regulated protein 78, and
heat shock proteins – can provide neuroprotection from aberrant proteins by facilitating proper folding and thus preventing
their aggregation. Our recent studies have linked nitrosative stress to protein misfolding and neuronal cell death. Here,
we present evidence for the hypothesis that nitric oxide contributes to degenerative conditions by S-nitrosylating specific chaperones or UPS proteins that would otherwise prevent accumulation of misfolded proteins.
Received 5 December 2006; received after revision 7 February 2007; accepted 15 March 2007 相似文献
998.
Talavera K Ninomiya Y Winkel C Voets T Nilius B 《Cellular and molecular life sciences : CMLS》2007,64(4):377-381
Daily experience tells us that temperature has a strong influence on how we taste. Despite the longstanding interest of many
specialists in this aspect of taste, we are only starting to understand the molecular mechanisms underlying the temperature
dependence of different taste modalities. Recent research has led to the identification of some strong thermosensitive molecules
in the taste transduction pathway. The cold activation of the epithelial Na+ channel and the heat activation of the taste variant of the vanilloid receptor (TRPV1t) may underlie the temperature dependence
of salt responses. Heat activation of the transient receptor potential channel TRPM5 explains the enhancement of sweet taste
perception by warm temperatures. Current development of methods to study taste cell physiology will help to determine the
contribution of other temperature-sensitive events in the taste transduction pathways. Vice versa, the analysis of the thermodynamic properties of these events may assist to unveil the nature of several taste processes.
Received 29 August 2006; received after revision 5 October 2006; accepted 20 November 2006 相似文献
999.
Deboer T 《Cellular and molecular life sciences : CMLS》2007,64(10):1227-1235
Sleep is investigated in many different ways, many different species and under many different circumstances. Modern sleep
research is a multidisciplinary venture. Therefore, this review cannot give a complete overview of all techniques used in
sleep research and sleep medicine. What it will try to do is to give an overview of widely applied techniques and exciting
new developments. Electroencephalography has been the backbone of sleep research and sleep medicine since its first application
in the 1930s. The electroencephalogram is still used but now combined with many different techniques monitoring body and brain
temperature, changes in brain and blood chemistry, or changes in brain functioning. Animal research has been very important
for progress in sleep research and sleep medicine. It provides opportunities to investigate the sleeping brain in ways not
possible in healthy volunteers. Progress in genomics has brought new insights in sleep regulation, the best example being
the discovery of hypocretin/orexin deficiency as the cause of narcolepsy. Gene manipulation holds great promise for the future
since it is possible not only to investigate the functions of different genes under normal conditions, but also to mimic human
pathology in much greater detail. 相似文献
1000.
Oshima T Sasaki M Kataoka H Miwa H Takeuchi T Joh T 《Cellular and molecular life sciences : CMLS》2007,64(23):3139-3147
Tight junctions (TJs) create a paracellular permeability barrier. Although reactive oxygen species have been implicated as
mediators of inflammation in inflammatory bowel diseases, their influence on the function of colonic epithelial TJs remains
unknown. Oxidative stress-mediated colonic epithelial permeability was significantly attenuated by a p38 mitogen-activated
protein (MAP) kinase inhibitor, SB203580. Although the amount of TJ proteins was not altered, hydrogen peroxide (H2O2) changed the localization of claudin-4 protein from an NP-40 insoluble fraction to a soluble fraction and from an apical
TJ to lateral membrane. The p38 MAP kinase inactivator Wip1 significantly attenuated phosphorylation of p38 MAP kinase, and
oxidative stress mediated permeability. H2O2-induced changes in claudin-4 localization were abolished by SB203580 pretreatment as well as Wip1-expressing adenovirus infection.
This is the first study to demonstrate that exogenous Wip1 functions to protect oxidative stress-mediated colonic mucosal
permeability and that H2O2-induced claudin-4 dislocalization is abolished by Wip1.
Received 14 June 2007; received after revision 8 October 2007; accepted 8 October 2007 相似文献