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91.
Yudkoff M Daikhin Y Nissim I Horyn O Lazarow A Luhovyy B Wehrli S Nissim I 《Neurochemistry international》2005,47(1-2):119-128
Our objective was to study brain amino acid metabolism in response to ketosis. The underlying hypothesis is that ketosis is associated with a fundamental change of brain amino acid handling and that this alteration is a factor in the anti-epileptic effect of the ketogenic diet. Specifically, we hypothesize that brain converts ketone bodies to acetyl-CoA and that this results in increased flux through the citrate synthetase reaction. As a result, oxaloacetate is consumed and is less available to the aspartate aminotransferase reaction; therefore, less glutamate is converted to aspartate and relatively more glutamate becomes available to the glutamine synthetase and glutamate decarboxylase reactions. We found in a mouse model of ketosis that the concentration of forebrain aspartate was diminished but the concentration of acetyl-CoA was increased. Studies of the incorporation of 13C into glutamate and glutamine with either [1-(13)C]glucose or [2-(13)C]acetate as precursor showed that ketotic brain metabolized relatively less glucose and relatively more acetate. When the ketotic mice were administered both acetate and a nitrogen donor, such as alanine or leucine, they manifested an increased forebrain concentration of glutamine and GABA. These findings supported the hypothesis that in ketosis there is greater production of acetyl-CoA and a consequent alteration in the equilibrium of the aspartate aminotransferase reaction that results in diminished aspartate production and potentially enhanced synthesis of glutamine and GABA. 相似文献
92.
Dong Min Dando Emily E. Kotliar Ilana Su Xiaoyang Dzikovski Boris Freed Jack H. Lin Hening 《Journal of biological inorganic chemistry》2019,24(6):777-782
JBIC Journal of Biological Inorganic Chemistry - Diphthamide, the target of diphtheria toxin, is a post-translationally modified histidine residue found in archaeal and eukaryotic translation... 相似文献
93.
Ilana Kronfeld Alexander Zsukerman Gila Kazimirsky Chaya Brodie 《Journal of neurochemistry》1995,65(4):1505-1514
Abstract: In this study we examined the effects of staurosporine, a potent inhibitor of protein kinase C (PKC), on the differentiation of C6 glial cells and on the expression and cellular distribution of specific PKC isoforms. Staurosporine reduced cell proliferation and induced distinctive changes in the morphological appearance of the cells to that characteristic of cells exhibiting astrocytic phenotypes. The differentiative effect of staurosporine was further indicated by the increased expression of two proteins related to astrocytic phenotypes, glial fibrillary acidic protein (GFAP) and glutamine synthetase. Thus, staurosporine induced a dose-dependent increase both in GFAP immunoreactivity and in the activity and protein levels of glutamine synthetase. Staurosporine also induced a decrease in the expression of PKC-β2 and an increase in that of PKC-γ. In addition, it induced translocation of PKC-ε from the membrane to the cytosol, whereas no differences were observed in the distribution of the other PKC isoforms. The results of our study indicate that staurosporine induced astrocytic phenotypes in glial cells and that changes in the expression and cellular distribution of these PKC isoforms may be related to astrocytic differentiation. 相似文献
94.
Metacaspases are cysteine specific proteases implicated in cell-signalling, stress acclimation and programmed cell death (PCD) pathways in plants, fungi, protozoa, bacteria and algae. We investigated metacaspase-like gene expression and biochemical activity in the bloom-forming, N2-fixing, marine cyanobacterium Trichodesmium, which undergoes PCD under low iron and high-light stress. We examined these patterns with respect to in-silico analyses of protein domain architectures that revealed a diverse array of regulatory domains within Trichodesmium metacaspases-like (TeMC) proteins. Experimental manipulations of laboratory cultures and oceanic surface blooms of Trichodesmium from the South Pacific Ocean triggered PCD under Fe-limitation and high light along with enhanced TeMC activity and upregulated expression of diverse TeMC representatives containing different regulatory domains. Furthermore, TeMC activity was significantly and positively correlated with caspase-like activity, which has been routinely observed to increase with PCD induction in Trichodesmium. Although both TeMC and caspase-like activities were stimulated upon PCD induction, inhibitor treatments of these proteolytic activities provided further evidence of largely distinct substrate specificities, even though some inhibitory crossover was observed. Our findings are the first results linking metacaspase expression and activity in PCD induced mortality in Trichodesmium. Yet, the role/s and specific activities of these different proteins remain to be elucidated. 相似文献
95.
Shmuel M. Rubinstein Ilana Kolodkin‐Gal Anna Mcloon Liraz Chai Roberto Kolter Richard Losick David A. Weitz 《Molecular microbiology》2012,86(2):426-436
Many bacteria organize themselves into structurally complex communities known as biofilms in which the cells are held together by an extracellular matrix. In general, the amount of extracellular matrix is related to the robustness of the biofilm. Yet, the specific signals that regulate the synthesis of matrix remain poorly understood. Here we show that the matrix itself can be a cue that regulates the expression of the genes involved in matrix synthesis in Bacillus subtilis. The presence of the exopolysaccharide component of the matrix causes an increase in osmotic pressure that leads to an inhibition of matrix gene expression. We further show that non‐specific changes in osmotic pressure also inhibit matrix gene expression and do so by activating the histidine kinase KinD. KinD, in turn, directs the phosphorylation of the master regulatory protein Spo0A, which at high levels represses matrix gene expression. Sensing a physical cue such as osmotic pressure, in addition to chemical cues, could be a strategy to non‐specifically co‐ordinate the behaviour of cells in communities composed of many different species. 相似文献
96.
Mandel I Paperna T Volkowich A Merhav M Glass-Marmor L Miller A 《Journal of cellular biochemistry》2012,113(7):2415-2423
The tight junctions (TJs) form continuous intracellular contacts, which help create selective barriers in epithelial and endothelial cell layers. The structures created by the TJs are very dynamic and can be rapidly remodeled in response to physiological and pathological signals. Claudin 5 is a membranal TJ protein which plays a critical role in determining the permeability of endothelial barriers. We describe the regulation of claudin 5 degradation by the ubiquitin-proteasome system (UPS). Our results indicate that claudin 5 has a relatively short half-life and can be polyubiquitinated on lysine 199. This ubiquitination appears to trigger the proteasome-dependent degradation of claudin 5. Other mechanisms also seem to be involved in the post-translational regulation of claudin 5, including a ubiquitin-independent and probably indirect lysosomal-dependent pathway. These findings provide evidence for the involvement of the UPS in the regulation of claudin 5 levels, and set the stage for further research to determine the involvement of this pathway in the modulation of the properties of TJs and cell-layer barriers. 相似文献
97.
Conjugated linoleic acid (CLA) describes a group of isomers of linoleic acid and has variable effects on bone formation and adiposity in vivo and in vitro. The variability may be due to individual effects of the predominant bioactive 9cis,11trans (9,11) and 10trans,12cis (10,12) CLA isomers. Osteoblasts and adipocytes are derived from mesenchymal stem cells (MSCs), and bone loss is accompanied by an increase in marrow adiposity. Osteoblast differentiation from MSCs requires activation of Wnt/β-catenin signaling by Wnt10b, which inhibits adipocyte differentiation by suppressing CCAAT/enhancer-binding protein (C/EBP) α. The objective of this study was to determine if 9,11 and 10,12 CLA affect osteoblast and adipocyte differentiation from MSCs and to determine whether any effects are associated with changes in Wnt10b and C/EBPα expression. Osteoblast differentiation was assessed by calcium deposition, alkaline phosphatase (ALP) activity, and the expression of Wnt10b, runx2 and osteocalcin. Adipocyte differentiation was assessed by oil red O staining and C/EBPα, PPARγ and FABP4 expression. Compared to vehicle, 9,11 CLA decreased calcium deposition (~15%), increased oil red O staining (~21-28%) and increased FABP4 (AP2) expression (~58-75%). In contrast, 10,12 CLA increased calcium deposition (~12-60%), ALP activity (~2.1-fold) and the expression of Wnt10b (~60-80%) and osteocalcin (~90%), but decreased oil red O staining (~30%) and the expression of C/EBPα (~24-38%) and PPARγ (~60%) (P<.05). Thus, our findings demonstrate isomer-specific effects of CLA on MSC differentiation, and suggest that 10,12 CLA may be a useful therapeutic agent to promote osteoblast differentiation from MSCs. 相似文献
98.
Ilana Anbinder Moshe Reuveni Raviv Azari Ilan Paran Sahadia Nahon Haviva Shlomo Lea Chen Moshe Lapidot Ilan Levin 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2009,119(3):519-530
Tomato yellow leaf curl virus (TYLCV) is devastating to tomato (Solanum lycopersicum) crops and resistant cultivars are highly effective in controlling the disease. The breeding line TY172, originating from
Solanum peruvianum, is highly resistant to TYLCV. To map quantitative trait loci (QTLs) controlling TYLCV resistance in TY172, appropriate segregating
populations were analyzed using 69 polymorphic DNA markers spanning the entire tomato genome. Results show that TYLCV resistance
in TY172 is controlled by a previously unknown major QTL, originating from the resistant line, and four additional minor QTLs.
The major QTL, we term Ty-5, maps to chromosome 4 and accounts for 39.7–46.6% of the variation in symptom severity among segregating plants (LOD score
33–35). The minor QTLs, originated either from the resistant or susceptible parents, were mapped to chromosomes 1, 7, 9 and
11, and contributed 12% to the variation in symptom severity in addition to Ty-5. 相似文献
99.
Experiments dating back to the 1940''s have led to the hypothesis that the brain is an immunologically privileged site, shielding its antigens from immune recognition. The paraneoplastic Hu syndrome provides a powerful paradigm for addressing this hypothesis; it is believed to develop because small cell lung cancers (SCLC) express the neuron-specific Hu protein. This leads to an Hu-specific tumor immune response that can develop into an autoimmune attack against neurons, presumably when immune privilege in the brain is breached. Interestingly, all SCLC express the onconeural HuD antigen, and clinically useful tumor immune responses can be detected in up to 20% of patients, yet the paraneoplastic neurologic syndrome is extremely rare. We found that HuD-specific CD8+ T cells are normally present in the mouse T cell repertoire, but are not expanded upon immunization, although they can be detected after in vitro expansion. In contrast, HuD-specific T cells could be directly activated in HuD null mice, without the need for in vitro expansion. Taken together, these results demonstrate robust tolerance to the neuronal HuD antigen in vivo, and suggest a re-evaluation of the current concept of immune privilege in the brain. 相似文献
100.