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51.
Release of calcium from intracellular stores of rat basophilic leukemia cells was monitored using the fluorescent probe chlortetracycline. The ability of chlortetracycline to indicate release from intracellular calcium stores was initially validated. The decrease of chlortetracycline fluorescence upon antigen-stimulation was not the result of secretion of granule-associated dye or of changes in the properties of the membranes. The chlortetracycline fluorescence signal was not influenced by Ca2+ influx across the plasma membrane. Results obtained from these chlortetracycline fluorescence measurements corresponded well with 45Ca efflux data, an indirect measurement of release of calcium from stores. Chlortetracycline was used to examine the rate of antigen-induced release of calcium from stores, the depletion of intracellular calcium stores by EGTA, and the relationship between the antigen-stimulated release of stored calcium and exocytosis. Chlortetracycline was shown to be a useful qualitative indicator for the release of intracellular calcium with a relatively rapid response time. 相似文献
52.
Megan N. Roberts Marita A. Wallace Alexey A. Tomilov Zeyu Zhou George R. Marcotte Dianna Tran Gabriella Perez Elena Gutierrez-Casado Shinichiro Koike Trina A. Knotts Denise M. Imai Stephen M. Griffey Kyoungmi Kim Kevork Hagopian Marissa Z. McMackin Fawaz G. Haj Keith Baar Gino A. Cortopassi Jose Alberto Lopez-Dominguez 《Cell metabolism》2018,27(5):1156
53.
Dror E. Warschawski Alexandre A. Arnold Isabelle Marcotte 《Biophysical journal》2018,114(6):1368-1376
A variety of lipids that differ by their chains and headgroups are found in biomembranes. In addition to studying the overall membrane phase, determination of the structure, dynamics, and headgroup conformation of individual lipids in the mixture would be of great interest. We have thus developed, to our knowledge, a new approach using solid-state 31P NMR, magic-angle spinning, and chemical-shift anisotropy (CSA) recoupling, using an altered version of the recoupling of chemical shift anisotropy (ROCSA) pulse sequence, here penned PROCSA. The resulting two-dimensional spectra allowed the simultaneous measurement of the isotropic chemical shift and CSA of each lipid headgroup, thus providing a valuable measure of its dynamics and structure. PROCSA was applied to mixtures of phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) in various relative proportions, to mimic bacterial membranes and assess the respective roles of lipids in shaping these bilayers. The results were interpreted in terms of membrane topology, lipid propensity to adopt various phases or conformations, and lipid-lipid miscibility. Our results showed that PG dictates the lipid behavior when present in a proportion of 20 mol % or more. A small proportion of PG is thus able to impose a bilayer structure to the hexagonal phase forming PE. We discuss the requirement for lipids, such as PE, to be able to adopt non-bilayer phases in a membrane. 相似文献
54.
Alexandre A. Arnold Jean-Philippe Bourgouin Bertrand Genard Dror E. Warschawski Réjean Tremblay Isabelle Marcotte 《Journal of biomolecular NMR》2018,70(2):123-131
In vivo or whole-cell solid-state NMR is an emerging field which faces tremendous challenges. In most cases, cell biochemistry does not allow the labelling of specific molecules and an in vivo study is thus hindered by the inherent difficulty of identifying, among a formidable number of resonances, those arising from a given molecule. In this work we examined the possibility of studying, by solid-state NMR, the model organism Chlamydomonas reinhardtii fully and non-specifically 13C labelled. The extension of NMR-based dynamic filtering from one-dimensional to two-dimensional experiments enabled an enhanced selectivity which facilitated the assignment of cell constituents. The number of resonances detected with these robust and broadly applicable experiments appears to be surprisingly sparse. Various constituents, notably galactolipids abundant in organelle membranes, carbohydrates from the cell wall, and starch from storage grains could be unambiguously assigned. Moreover, the dominant crystal form of starch could be determined in situ. This work illustrates the feasibility and caveats of using solid-state NMR to study intact non-specifically 13C labelled micro-organisms. 相似文献
55.
Tricia L. May-Dracka Robert Arduini Andrea Bertolotti-Ciarlet Govinda Bhisetti Margot Brickelmaier Ellen Cahir-McFarland Istvan Enyedy Jason D. Fontenot Thomas Hesson Kevin Little Joe Lyssikatos Douglas Marcotte Timothy McKee Paramasivam Murugan Thomas Patterson Hairuo Peng Mia Rushe Laura Silvian Linda C. Burkly 《Bioorganic & medicinal chemistry letters》2018,28(10):1964-1971
Germinal center kinase-like kinase (GLK, also known as MAP4K3) has been hypothesized to have an effect on key cellular activities, including inflammatory responses. GLK is required for activation of protein kinase C-θ (PKCθ) in T cells. Controlling the activity of T helper cell responses could be valuable for the treatment of autoimmune diseases. This approach circumvents previous unsuccessful approaches to target PKCθ directly. The use of structure based drug design, aided by the first crystal structure of GLK, led to the discovery of several inhibitors that demonstrate potent inhibition of GLK biochemically and in relevant cell lines. 相似文献
56.
R. Turcotte L. Kiteala J. E. Marcotte H. Perrault 《European journal of applied physiology and occupational physiology》1997,75(5):425-430
The purpose of this investigation was to examine if exercise-induced arterial oxyhemoglobin desaturation selectively observed
in highly trained endurance athletes could be related to differences in the pulmonary diffusing capacity (D
L) measured during exercise. The D
L of 24 male endurance athletes was measured using a 3-s breath-hold carbon monoxide procedure (to give D
LCO) at rest as well as during cycling at 60% and 90% of these previously determined O2max. Oxyhemoglobin saturation (S
aO2%) was monitored throughout both exercise protocols using an Ohmeda Biox II oximeter. Exercise-induced oxyhemoglobin desaturation
(DS) (S
aO2% < 91% at O2max) was observed in 13 subjects [88.2 (0.6)%] but not in the other 11 nondesaturation subjects [NDS: 92.9 (0.4)%] (P ≤ 0.05), although O2max was not significantly different between the groups [DS: 4.34 (0.65) l / min vs NDS: 4.1 (0.49) l / min]. At rest, no differences
in either D
LCO [m1 CO · mmHg−1 · min−1: 41.7 (1.7) (DS) vs 41.1 (1.8) (NDS)], D
LCO /
A
[8.2 (0.4) (DS) vs 7.3 (0.9) (NDS)], MVV [l / min: 196.0 (10.4) (DS) vs 182.0 (9.9) (NDS)] or FEV1/FVC [86.3 (2.2) (DS) vs 82.9 (4.7) (NDS)] were found between groups (P ≥ 0.05). However,
E /O2 at O2max was lower in the DS group [33.0 (1.1)] compared to the NDS group [36.8 (1.5)] (P ≤ 0.05). Exercise D
LCO (m1 CO · mmHg−1 · min−1 ) was not different between groups at either 60% O2max [DS: 55.1 (1.4) vs NDS: 57.2 (2.1)] or at 90% O2max [DS: 61.0 (1.8) vs NDS: 61.4 (2.9)]. A significant relationship (r = 0.698) was calculated to occur between S
aO2% and
E /O2 during maximal exercise. The present findings indicate that the exercise-induced oxyhemoglobin desaturation seen during submaximal
and near-maximal exercise is not related to differences in D
L, although during maximal exercise S
aO2 may be limited by a relatively lower exercise ventilation.
Accepted: 25 September 1996 相似文献
57.
Mycobacterium smegmatis is a fast-growing model mycobacterial system that shares many features with the pathogenic Mycobacterium tuberculosis while allowing practical proteomics analysis. With the use of shotgun-style mass spectrometry, we provide a large-scale analysis of the M. smegmatis proteomic response to the anti-tuberculosis (TB) drugs isoniazid, ethambutol, and 5-chloropyrazinamide and elucidate the drugs' systematic effects on mycobacterial proteins. A total of 2550 proteins were identified with approximately 5% false-positive identification rate across 60 experiments, representing approximately 40% of the M. smegmatis proteome ( approximately 6500 proteins). Protein differential expression levels were estimated from the shotgun proteomics data, and 485 proteins showing altered expression levels in response to drugs were identified at a 99% confidence level. Proteomic comparison of anti-TB drug responses shows that translation, cell cycle control, and energy production are down-regulated in all three drug treatments. In contrast, systems related to the drugs' targets, such as lipid, amino acid, and nucleotide metabolism, show specific protein expression changes associated with a particular drug treatment. We identify proteins involved in target pathways for the three drugs and infer putative targets for 5-chloropyrazinamide. 相似文献
58.
Spidroin N-terminal domain promotes a pH-dependent association of silk proteins during self-assembly
Spider silks are spun from concentrated solutions of spidroin proteins. The appropriate timing of spidroin assembly into organized fibers must be highly regulated to avoid premature fiber formation. Chemical and physical signals presented to the silk proteins as they pass from the ampulle and through the tapered duct include changes in ionic environment and pH as well as the introduction of shear forces. Here, we show that the N-terminal domain of spidroins from the major ampullate gland (MaSp-NTDs) for both Nephila and Latrodectus spiders associate noncovalently as homodimers. The MaSp-NTDs are highly pH-responsive and undergo a structural transition in the physiological pH range of the spider duct. Tryptophan fluorescence of the MaSp-NTDs reveals a change in conformation when pH is decreased, and the pH at which the transition occurs is determined by the amount and type of salt present. Size exclusion chromatography and pulldown assays both indicate that the lower pH conformation is associated with a significantly increased MaSp-NTD homodimer stability. By transducing the duct pH signal into specific protein-protein interactions, this conserved spidroin domain likely contributes significantly to the silk-spinning process. Based on these results, we propose a model of spider silk assembly dynamics as mediated through the MaSp-NTD. 相似文献
59.
Curtin ML Heyman HR Frey RR Marcotte PA Glaser KB Jankowski JR Magoc TJ Albert DH Olson AM Reuter DR Bouska JJ Montgomery DA Palma JP Donawho CK Stewart KD Tse C Michaelides MR 《Bioorganic & medicinal chemistry letters》2012,22(14):4750-4755
In an effort to identify kinase inhibitors with dual KDR/Aurora B activity and improved aqueous solubility compared to the Abbott dual inhibitor ABT-348, a series of novel pyrazole pyrimidines structurally related to kinase inhibitor AS703569 were prepared. SAR work provided analogs with significant cellular activity, measureable aqueous solubility and moderate antitumor activity in a mouse tumor model after weekly ip dosing. Unfortunately these compounds were pan-kinase inhibitors that suffered from narrow therapeutic indices which prohibited their use as antitumor agents. 相似文献
60.
Jody Corey-Bloom Tanya Wolfson Anthony Gamst Shelia Jin Thomas D. Marcotte Heather Bentley Ben Gouaux 《CMAJ》2012,184(10):1143-1150