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181.
New type of linear cholesterol-like molecules based on cholesterol extended by attachment of etienic acid derivatives was designed and oligosteroids with two to four units were synthesized. Amide bond was used for inter steroid connections and 1-hydroxybenzotriazole active ester method was adapted for their formations. Use of disteroids as larger building blocks was applied. 相似文献
182.
Kukavica Biljana; Mojovic Milos; Vuccinic Zeljko; Maksimovic Vuk; Takahama Umeo; Jovanovic Sonja Veljovic 《Plant & cell physiology》2009,50(2):304-317
The hydroxyl radical produced in the apoplast has been demonstratedto facilitate cell wall loosening during cell elongation. Cellwall-bound peroxidases (PODs) have been implicated in hydroxylradical formation. For this mechanism, the apoplast or cellwalls should contain the electron donors for (i) H2O2 formationfrom dioxygen; and (ii) the POD-catalyzed reduction of H2O2to the hydroxyl radical. The aim of the work was to identifythe electron donors in these reactions. In this report, hydroxylradical (·OH) generation in the cell wall isolated frompea roots was detected in the absence of any exogenous reductants,suggesting that the plant cell wall possesses the capacity togenerate ·OH in situ. Distinct POD and Mn-superoxidedismutase (Mn-SOD) isoforms different from other cellular isoformswere shown by native gel electropho-resis to be preferably boundto the cell walls. Electron paramagnetic resonance (EPR) spectroscopyof cell wall isolates containing the spin-trapping reagent,5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO),was used for detection of and differentiation between ·OHand the superoxide radical (O2–·). The data obtainedusing POD inhibitors confirmed that tightly bound cell wallPODs are involved in DEPMPO/OH adduct formation. A decreasein DEPMPO/OH adduct formation in the presence of H2O2 scavengersdemonstrated that this hydroxyl radical was derived from H2O2.During the generation of ·OH, the concentration of quinhydronestructures (as detected by EPR spectroscopy) increased, suggestingthat the H2O2 required for the formation of ·OH in isolatedcell walls is produced during the reduction of O2 by hydroxycinnamicacids. Cell wall isolates in which the proteins have been denaturated(including the endogenous POD and SOD) did not produce ·OH.Addition of exogenous H2O2 again induced the production of ·OH,and these were shown to originate from the Fenton reaction withtightly bound metal ions. However, the appearance of the DEPMPO/OOHadduct could also be observed, due to the production of O2–·when endogenous SOD has been inactivated. Also, O2–·was converted to ·OH in an in vitro horseradish peroxidase(HRP)/H2O2 system to which exogenous SOD has been added. Takentogether with the discovery of the cell wall-bound Mn-SOD isoform,these results support the role of such a cell wall-bound SODin the formation of ·OH jointly with the cell wall-boundPOD. According to the above findings, it seems that the hydroxycinnamicacids from the cell wall, acting as reductants, contribute tothe formation of H2O2 in the presence of O2 in an autocatalyticmanner, and that POD and Mn-SOD coupled together generate ·OHfrom such H2O2. 相似文献
183.
184.
Boydston-White S Romeo M Chernenko T Regina A Miljković M Diem M 《Biochimica et biophysica acta》2006,1758(7):908-914
We have previously reported spectral differences for cells at different stages of the eukaryotic cell division cycle. These differences are due to the drastic biochemical and morphological changes that occur as a consequence of cell proliferation. We correlate these changes in FTIR absorption and Raman spectra of individual cells with their biochemical age (or phase in the cell cycle), determined by immunohistochemical staining to detect the appearance (and subsequent disappearance) of cell-cycle-specific cyclins, and/or the occurrence of DNA synthesis. Once spectra were correlated with their cells' staining patterns, we used methods of multivariate statistics to analyze the changes in cellular spectra as a function of cell cycle phase. 相似文献
185.
Watkins TC Zelinka LM Kesic M Ansevin CF Walker GR 《Journal of cellular biochemistry》2006,99(1):79-87
Novel forms of contractile regulation observed in skeletal muscle are evident in neuromuscular diseases like rippling muscle disease (RMD). Previous studies of an autoimmune form of RMD (ARMD) identified a very high molecular weight skeletal muscle protein antigen recognized by ARMD patient antisera. This study utilized ARMD and myasthenia gravis (MG) patient antisera, to screen a human skeletal muscle cDNA library that subsequently identified proteins that could play a role in ARMD. Based on nucleotide sequence analysis, three distinct ARMD antigens were identified: titin Isoform N2A, ATP synthase 6, and PPP1R3 (protein phosphatase 1 regulatory subunit 3). The region of titin identified by ARMD antisera is distinct from the main immunogenic region (MIR) recognized by classical MG antibodies. Sera from classical MG patient identifies an expressed sequence corresponding to the titin MIR. Although the mechanism of antibody penetration is not known, previous studies have shown that rippling muscle antibodies affect the contractile machinery of myofibers resulting in mechanical sensitivity. Titin's role as a modulator of muscle contractility makes it a potential target in understanding muscle mechanosensitive regulation. 相似文献
186.
Tang H Arnold RJ Alves P Xun Z Clemmer DE Novotny MV Reilly JP Radivojac P 《Bioinformatics (Oxford, England)》2006,22(14):e481-e488
We propose here a new concept of peptide detectability which could be an important factor in explaining the relationship between a protein's quantity and the peptides identified from it in a high-throughput proteomics experiment. We define peptide detectability as the probability of observing a peptide in a standard sample analyzed by a standard proteomics routine and argue that it is an intrinsic property of the peptide sequence and neighboring regions in the parent protein. To test this hypothesis we first used publicly available data and data from our own synthetic samples in which quantities of model proteins were controlled. We then applied machine learning approaches to demonstrate that peptide detectability can be predicted from its sequence and the neighboring regions in the parent protein with satisfactory accuracy. The utility of this approach for protein quantification is demonstrated by peptides with higher detectability generally being identified at lower concentrations over those with lower detectability in the synthetic protein mixtures. These results establish a direct link between protein concentration and peptide detectability. We show that for each protein there exists a level of peptide detectability above which peptides are detected and below which peptides are not detected in an experiment. We call this level the minimum acceptable detectability for identified peptides (MDIP) which can be calibrated to predict protein concentration. Triplicate analysis of a biological sample showed that these MDIP values are consistent among the three data sets. 相似文献
187.
Among mental disorders, mental retardation has been shown to be caused by various factors including a large array of genetic mutations. On the basis of remarkable progress, the emerging view is that defects in the regulation of synaptic activity and morphogenesis of dendritic spines are apparently common features associated with mutations in several genes implicated in mental retardation. In this review, we will discuss X-linked MR-related gene products that are potentially involved in the normal structure and function of the synapses, with a particular focus on pre- and/or post-synaptic plasticity mechanisms. Progress in understanding the underlying conditions leading to mental retardation will undoubtedly be gained from a closer collaboration of geneticists, physiologists and cognitive neuroscientists, which should enable the establishment of standardized approaches. 相似文献
188.
Eberhardt MJ Filipovic MR Leffler A de la Roche J Kistner K Fischer MJ Fleming T Zimmermann K Ivanovic-Burmazovic I Nawroth PP Bierhaus A Reeh PW Sauer SK 《The Journal of biological chemistry》2012,287(34):28291-28306
Neuropathic pain can develop as an agonizing sequela of diabetes mellitus and chronic uremia. A chemical link between both conditions of altered metabolism is the highly reactive compound methylglyoxal (MG), which accumulates in all cells, in particular neurons, and leaks into plasma as an index of the severity of the disorder. The electrophilic structure of this cytotoxic ketoaldehyde suggests TRPA1, a receptor channel deeply involved in inflammatory and neuropathic pain, as a molecular target. We demonstrate that extracellularly applied MG accesses specific intracellular binding sites of TRPA1, activating inward currents and calcium influx in transfected cells and sensory neurons, slowing conduction velocity in unmyelinated peripheral nerve fibers, and stimulating release of proinflammatory neuropeptides from and action potential firing in cutaneous nociceptors. Using a model peptide of the N terminus of human TRPA1, we demonstrate the formation of disulfide bonds based on MG-induced modification of cysteines as a novel mechanism. In conclusion, MG is proposed to be a candidate metabolite that causes neuropathic pain in metabolic disorders and thus is a promising target for medicinal chemistry. 相似文献
189.
Muscarinic receptor activation facilitates the induction of synaptic plasticity and enhances cognitive function. However, the specific muscarinic receptor subtype involved and the critical intracellular signaling pathways engaged have remained controversial. Here, we show that the recently discovered highly selective allosteric M(1) receptor agonist 77-LH-28-1 facilitates long-term potentiation (LTP) induced by theta burst stimulation at Schaffer collateral synapses in the hippocampus. Similarly, release of acetylcholine by stimulation of cholinergic fibers facilitates LTP via activation of M(1) receptors. N-methyl-D-aspartate receptor (NMDAR) opening during theta burst stimulation was enhanced by M(1) receptor activation, indicating this is the mechanism for LTP facilitation. M(1) receptors were found to enhance NMDAR activation by inhibiting SK channels that otherwise act to hyperpolarize postsynaptic spines and inhibit NMDAR opening. Thus, we describe a mechanism where M(1) receptor activation inhibits SK channels, allowing enhanced NMDAR activity and leading to a facilitation of LTP induction in the hippocampus. 相似文献
190.