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71.
72.
Background
Mucolipidosis Type IV is currently characterized as a lysosomal storage disorder with defects that include corneal clouding, achlorhydria and psychomotor retardation. MCOLN1, the gene responsible for this disease, encodes the protein mucolipin-1 that belongs to the "Transient Receptor Potential" family of proteins and has been shown to function as a non-selective cation channel whose activity is modulated by pH. Two cell biological defects that have been described in MLIV fibroblasts are a hyperacidification of lysosomes and a delay in the exit of lipids from lysosomes. 相似文献73.
Tulika Sarma Athanasia Koutsouris Jiang Zhu Yu Aleksandar Krbanjevic Thomas J. Hope Mark M. Rasenick 《The Journal of biological chemistry》2015,290(16):10045-10056
Signals that activate the G protein Gαs and promote neuronal differentiation evoke Gαs internalization in rat pheochromocytoma (PC12) cells. These agents also significantly increase Gαs association with microtubules, resulting in an increase in microtubule dynamics because of the activation of tubulin GTPase by Gαs. To determine the function of Gαs/microtubule association in neuronal development, we used real-time trafficking of a GFP-Gαs fusion protein. GFP-Gαs concentrates at the distal end of the neurites in differentiated living PC12 cells as well as in cultured hippocampal neurons. Gαs translocates to specialized membrane compartments at tips of growing neurites. A dominant-negative Gα chimera that interferes with Gαs binding to tubulin and activation of tubulin GTPase attenuates neurite elongation and neurite number both in PC12 cells and primary hippocampal neurons. This effect is greatest on differentiation induced by activated Gαs. Together, these data suggest that activated Gαs translocates from the plasma membrane and, through interaction with tubulin/microtubules in the cytosol, is important for neurite formation, development, and outgrowth. Characterization of neuronal G protein dynamics and their contribution to microtubule dynamics is important for understanding the molecular mechanisms by which G protein-coupled receptor signaling orchestrates neuronal growth and differentiation. 相似文献
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75.
Zhao J Del Bigio MR Weiler HA 《Prostaglandins, leukotrienes, and essential fatty acids》2011,84(1-2):63-70
Maternal diabetes may compromise infant arachidonic acid (AA) status and development. This study tested if maternal AA supplementation improves neurodevelopment in adult offspring. Rat dams were randomized into 6 groups: Saline-Placebo, streptozotocin-induced diabetes with glucose controlled at <13mmol/L, or poorly controlled at 13-20mmol/L using insulin; and fed either a Control or AA (0.5% fat) diet throughout reproduction. Weaned-offspring were fed regular chow to 12 weeks of age. Testing included exploratory behavior, rota rod and water maze (WM). Poorly controlled offspring showed longer (p≤0.018) escape-latency on testing-day 1 WM but not thereafter (p>0.05). Maternal glucose concentration positively correlated with (p=0.006) male offspring testing-day 1 WM latency. The AA-diet offspring performed better in WM and rota rod (p≤0.032) and showed higher exploratory behavior (p=0.008) than Control-diet offspring. These data suggest maternal hyperglycemia has longstanding consequences to initial stages of learning in the offspring. Maternal AA supplementation and training positively influence learning outcomes. 相似文献
76.
TRA-8, a monoclonal antibody to death receptor 5 induces apoptosis in various cancer cells; however, the degree of sensitivity varies from highly sensitive to resistant. We have previously shown that resistance to TRA-8 can be reversed by using chemotherapeutic agents, but the mechanism underlying this sensitization was not fully understood. Here, we examined the combination of TRA-8 with doxorubicin or bortezomib in breast cancer cells. In TRA-8-resistant BT-474 and T47D cells, both chemotherapy agents synergistically sensitized cells to TRA-8 cytotoxicity with enhanced activation of apoptosis shown by cleavage of caspases and PARP, reduced Bid, increased proapoptotic Bcl-2 proteins, and increased mitochondrial membrane depolarization. Doxorubicin or bortezomib combined with TRA-8 also reduced Bcl-XL and X-linked inhibitors of apoptosis (XIAP) in treated cells. Furthermore, targeting these proteins with pharmacologic modulators, AT-101, BH3I-2' and AT-406, produced sensitization to TRA-8. TRA-8 combined with AT-101 or BH3I-2', inhibitors of antiapoptotic Bcl-2 proteins, produced synergistic cytotoxicity against ZR-75-1, BT-474, and T47D cells. The IAP-targeting compound, AT-406, was synergistic with TRA-8 in BT-474 cells, and to a lesser extent T47D cells. Activation of the intrinsic apoptotic pathway was a common mechanism associated with sensitization of TRA-8-resistant breast cancer cell lines. Collectively, these studies show that the Bcl-2 and IAP families of proteins are involved in TRA-8 and chemotherapy resistance via their modulation of the intrinsic apoptotic pathway. Targeting these proteins with novel agents sensitized TRA-8-resistant breast cancer cells, suggesting this approach may represent a potent therapeutic strategy in the treatment of breast cancer. 相似文献
77.
The aim of this study is to investigate whether PI3K (phosphatidylinositol-3-kinase) is involved in IL-1β (interleukin-1β)-induced IL-6 production in A549 (human lung adenocarcinoma epithelial cell) and human RASF (rheumatoid arthritis synovial fibroblast). PI3K inhibitor, LY294002 significantly reduced IL-1β-induced IL-6 production in A549 cells but not in RASF, indicating that IL-1β-induced IL-6 production was partially mediated by PI3Kin A549 cells but not in RASF. siRNA (small interfering RNA) of IRAK4 (IL-1 receptor-associated kinase 4) treatment decreased IRAK4 mRNA level by up to 90% in A549 cells. In this condition, IL-1β-induced increase of IL-6 mRNA and protein level was decreased by up to 93% and 70%, respectively. Furthermore, the combination of IRAK4 siRNA and LY294002 treatment decreased protein induction level of IL-6 in A549 cells compared with that of IRAK4 siRNA or LY294002 alone. These results indicate that IL-1β-induced IL-6 production in A549 cells is mediated by both PI3K and IRAK4 and suggest that involvement of PI3K in the IL-1-induced IL-6 production is cell type specific. 相似文献
78.
Copeland A O'Connor K Lucas S Lapidus A Berry KW Detter JC Del Rio TG Hammon N Dalin E Tice H Pitluck S Bruce D Goodwin L Han C Tapia R Saunders E Schmutz J Brettin T Larimer F Land M Hauser L Vargas C Nieto JJ Kyrpides NC Ivanova N Göker M Klenk HP Csonka LN Woyke T 《Standards in genomic sciences》2011,5(3):379-388
Chromohalobacter salexigens is one of nine currently known species of the genus Chromohalobacter in the family Halomonadaceae. It is the most halotolerant of the so-called 'moderately halophilic bacteria' currently known and, due to its strong euryhaline phenotype, it is an established model organism for prokaryotic osmoadaptation. C. salexigens strain 1H11(T) and Halomonas elongata are the first and the second members of the family Halomonadaceae with a completely sequenced genome. The 3,696,649 bp long chromosome with a total of 3,319 protein-coding and 93 RNA genes was sequenced as part of the DOE Joint Genome Institute Program DOEM 2004. 相似文献
79.
Chertkov O Brown PJ Kysela DT de Pedro MA Lucas S Copeland A Lapidus A Del Rio TG Tice H Bruce D Goodwin L Pitluck S Detter JC Han C Larimer F Chang YJ Jeffries CD Land M Hauser L Kyrpides NC Ivanova N Ovchinnikova G Tindall BJ Göker M Klenk HP Brun YV 《Standards in genomic sciences》2011,5(3):287-297
The family Hyphomonadaceae within the Alphaproteobacteria is largely comprised of bacteria isolated from marine environments with striking morphologies and an unusual mode of cell growth. Here, we report the complete genome sequence Hirschia baltica, which is only the second a member of the Hyphomonadaceae with a published genome sequence. H. baltica is of special interest because it has a dimorphic life cycle and is a stalked, budding bacterium. The 3,455,622 bp long chromosome and 84,492 bp plasmid with a total of 3,222 protein-coding and 44 RNA genes were sequenced as part of the DOE Joint Genome Institute Program CSP 2008. 相似文献
80.
Chertkov O Sikorski J Nolan M Lapidus A Lucas S Del Rio TG Tice H Cheng JF Goodwin L Pitluck S Liolios K Ivanova N Mavromatis K Mikhailova N Ovchinnikova G Pati A Chen A Palaniappan K Djao OD Land M Hauser L Chang YJ Jeffries CD Brettin T Han C Detter JC Rohde M Göker M Woyke T Bristow J Eisen JA Markowitz V Hugenholtz P Klenk HP Kyrpides NC 《Standards in genomic sciences》2011,4(1):13-22
Thermomonospora curvata Henssen 1957 is the type species of the genus Thermomonospora. This genus is of interest because members of this clade are sources of new antibiotics, enzymes, and products with pharmacological activity. In addition, members of this genus participate in the active degradation of cellulose. This is the first complete genome sequence of a member of the family Thermomonosporaceae. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 5,639,016 bp long genome with its 4,985 protein-coding and 76 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献