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121.
Reactive oxygen species are important mediators of taurine release from skeletal muscle cells 总被引:3,自引:0,他引:3
Ørtenblad N Young JF Oksbjerg N Nielsen JH Lambert IH 《American journal of physiology. Cell physiology》2003,284(6):C1362-C1373
The present study illustrates elements ofthe signal cascades involved in the activation of taurine effluxpathways in myotubes derived from skeletal muscle cells. Exposingprimary skeletal muscle cells, loaded with 14C-taurine, to1) hypotonic media, 2) the phospholipaseA2 (PLA2) activator melittin, 3)anoxia, or 4) lysophosphatidyl choline (LPC) causes anincrease in 14C-taurine release and a concomitantproduction of reactive oxygen species (ROS). The antioxidants butulatedhydroxy toluene and vitamin E inhibit the taurine efflux after cellswelling, anoxia, and addition of LPC. The muscle cells possess twoseparate taurine efflux pathways, i.e., a swelling- andmelittin-induced pathway that requires 5-lipoxygenase activity foractivation and a LPC-induced pathway. The two pathways aredistinguished by their opposing sensitivity toward the anion channelblocker DIDS and cholesterol. These data provide evidence forPLA2 products and ROS as key mediators of the signalcascade leading to taurine efflux in muscle. 相似文献
122.
Poi MJ Tomaszewski JW Yuan C Dunlap CA Andersen NH Gelb MH Tsai MD 《Journal of molecular biology》2003,329(5):997-1009
This work describes in-depth NMR characterization of a unique low-barrier hydrogen bond (LBHB) between an active site residue from the enzyme and a bound inhibitor: the complex between secreted phospholipase A(2) (sPLA(2), from bee venom and bovine pancreas) and a transition-state analog inhibitor HK32. A downfield proton NMR resonance, at 17-18 ppm, was observed in the complex but not in the free enzyme. On the basis of site-specific mutagenesis and specific 15N-decoupling, this downfield resonance was assigned to the active site H48, which is part of the catalytic dyad D99-H48. These results led to a hypothesis that the downfield resonance represents the proton (H(epsilon 2) of H48) involved in the H-bonding between D99 and H48, in analogy with serine proteases. However, this was shown not to be the case by use of the bovine enzyme labeled with specific [15N(epsilon 2)]His. Instead, the downfield resonance arises from H(delta1) of H48, which forms a hydrogen bond with a non-bridging phosphonate oxygen of the inhibitor. Further studies showed that this proton displays a fractionation factor of 0.62(+/-0.06), and an exchange rate protection factor of >100 at 285 K and >40 at 298 K, which are characteristic of a LBHB. The pK(a) of the imidazole ring of H48 was shown to be shifted from 5.7 for the free enzyme to an apparent value of 9.0 in the presence of the inhibitor. These properties are very similar to those of the Asp em leader His LBHBs in serine proteases. Possible structural bases and functional consequences for the different locations of the LBHB between these two types of enzymes are discussed. The results also underscore the importance of using specific isotope labeling, rather than extrapolation of NMR results from other enzyme systems, to assign the downfield proton resonance to a specific hydrogen bond. Although our studies did not permit the strength of the LBHB to be accurately measured, the data do not provide support for an unusually strong hydrogen bond strength (i.e. >10 kcal/mol). 相似文献
123.
Bonefeld CM Rasmussen AB Lauritsen JP von Essen M Ødum N Andersen PS Geisler C 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(6):3003-3009
One of the earliest events following TCR triggering is TCR down-regulation. However, the mechanisms behind TCR down-regulation are still not fully known. Some studies have suggested that only directly triggered TCR are internalized, whereas others studies have indicated that, in addition to triggered receptors, nonengaged TCR are also internalized (comodulated). In this study, we used transfected T cells expressing two different TCR to analyze whether comodulation took place. We show that TCR triggering by anti-TCR mAb and peptide-MHC complexes clearly induced internalization of nonengaged TCR. By using a panel of mAb against the Ti beta chain, we demonstrate that the comodulation kinetics depended on the affinity of the ligand. Thus, high-affinity mAb (K(D) = 2.3 nM) induced a rapid but reversible comodulation, whereas low-affinity mAb (K(D) = 6200 nM) induced a slower but more permanent type of comodulation. Like internalization of engaged TCR, comodulation was dependent on protein tyrosine kinase activity. Finally, we found that in contrast to internalization of engaged TCR, comodulation was highly dependent on protein kinase C activity and the CD3 gamma di-leucine-based motif. Based on these observations, a physiological role of comodulation is proposed and the plausibility of the TCR serial triggering model is discussed. 相似文献
124.
125.
Sørensen OE Gram L Johnsen AH Andersson E Bangsbøll S Tjabringa GS Hiemstra PS Malm J Egesten A Borregaard N 《The Journal of biological chemistry》2003,278(31):28540-28546
The human cathelicidin, hCAP-18, is expressed both in neutrophils and in epithelial cells. hCAP-18 is processed to the antimicrobial peptide LL-37 by proteinase 3 in neutrophils. hCAP-18 is highly expressed in the epididymis with a subsequent high concentration in seminal plasma where the protein is present in its unprocessed and antimicrobially inactive form. We report here that hCAP-18 in seminal plasma is processed to generate a 38-amino acid antimicrobial peptide ALL-38 by the prostate-derived protease gastricsin when incubated at a pH corresponding to the vaginal pH. In accordance with this, seminal plasma derived hCAP-18 was found in its processed form in the vagina following sexual intercourse. The antimicrobial activity of ALL-38 against a variety of microorganisms tested is equal to that of LL-37. This enzymatic activation of a proantimicrobial substance in seminal plasma following exposure to the vaginal milieu represents a novel mechanism to prevent infection following sexual intercourse. 相似文献
126.
Pedersen CB Bross P Winter VS Corydon TJ Bolund L Bartlett K Vockley J Gregersen N 《The Journal of biological chemistry》2003,278(48):47449-47458
Short chain acyl-CoA dehydrogenase (SCAD) deficiency is an inborn error of the mitochondrial fatty acid metabolism caused by rare variations as well as common susceptibility variations in the SCAD gene. Earlier studies have shown that a common variant SCAD protein (R147W) was impaired in folding, and preliminary experiments suggested that the variant protein displayed prolonged association with chaperonins and delayed formation of active enzyme. Accordingly, the molecular pathogenesis of SCAD deficiency may rely on intramitochondrial protein quality control mechanisms, including degradation and aggregation of variant SCAD proteins. In this study we investigated the processing of a set of disease-causing variant SCAD proteins (R22W, G68C, W153R, R359C, and Q341H) and two common variant proteins (R147W and G185S) that lead to reduced SCAD activity. All SCAD proteins, including the wild type, associate with mitochondrial hsp60 chaperonins; however, the variant SCAD proteins remained associated with hsp60 for prolonged periods of time. Biogenesis experiments at two temperatures revealed that some of the variant proteins (R22W, G68C, W153R, and R359C) caused severe misfolding, whereas others (R147W, G185S, and Q341H) exhibited a less severe temperature-sensitive folding defect. Based on the magnitude of in vitro defects, these SCAD proteins are characterized as folding-defective variants and mild folding variants, respectively. Pulse-chase experiments demonstrated that the variant SCAD proteins either triggered proteolytic degradation by mitochondrial proteases or, especially at elevated temperature, aggregation of non-native conformers. The latter finding may indicate that accumulation of aggregated SCAD proteins may play a role in the pathogenesis of SCAD deficiency. 相似文献
127.
Valero-Cuevas FJ Smaby N Venkadesan M Peterson M Wright T 《Journal of biomechanics》2003,36(2):265-270
We have developed a method to quantify the dynamic interaction between fingertip force magnitude (strength) and directional control (dexterity) during pinch with a novel strength-dexterity (S-D) test based on the principle of buckling of compression springs. The test consists of asking participants to use key and opposition pinch to attempt to fully compress springs, in random order, with a wide range of combinations of strength and dexterity requirements. The minimum force required to fully compress the spring and the propensity of the spring to buckle define the strength and dexterity requirements, respectively. The S-D score for each pinch style was the sum of the strength values of all springs successfully compressed fully. We tested 3 participant groups: 18 unimpaired young adults (40yr), and 14 adults diagnosed with carpo-metacarpal osteoarthritis (CMC OA) (>or = 36yr). We investigated the repeatability of the S-D test with 74 springs by testing 14 young adults twice on different days. The per-spring repeatability across subjects was >or = 94%. A minimum performance score for young adults was found as they all could compress a subset of 39 springs. Using this subset of springs, we compared the ability of the S-D score vs. maximal pinch force values to distinguish unimpaired hands from those with CMC OA of the thumb. The score for this 39-spring S-D test distinguished between CMC OA and asymptomatic older adults, whereas pinch meter readings did not (p<0.05). We conclude that the S-D test is repeatable and applicable to clinical research. We propose including the S-D test in studies aiming to quantify impairment and compare treatment outcomes in orthopaedic and neurological afflictions that degrade dynamic manipulation. 相似文献
128.
Distribution patterns of postmortem damage in human mitochondrial DNA 总被引:12,自引:0,他引:12
Gilbert MT Willerslev E Hansen AJ Barnes I Rudbeck L Lynnerup N Cooper A 《American journal of human genetics》2003,72(1):32-47
The distribution of postmortem damage in mitochondrial DNA retrieved from 37 ancient human DNA samples was analyzed by cloning and was compared with a selection of published animal data. A relative rate of damage (rho(v)) was calculated for nucleotide positions within the human hypervariable region 1 (HVR1) and cytochrome oxidase subunit III genes. A comparison of damaged sites within and between the regions reveals that damage hotspots exist and that, in the HVR1, these correlate with sites known to have high in vivo mutation rates. Conversely, HVR1 subregions with known structural function, such as MT5, have lower in vivo mutation rates and lower postmortem-damage rates. The postmortem data also identify a possible functional subregion of the HVR1, termed "low-diversity 1," through the lack of sequence damage. The amount of postmortem damage observed in mitochondrial coding regions was significantly lower than in the HVR1, and, although hotspots were noted, these did not correlate with codon position. Finally, a simple method for the identification of incorrect archaeological haplogroup designations is introduced, on the basis of the observed spectrum of postmortem damage. 相似文献
129.
Xie L Lee SY Andersen JN Waters S Shen K Guo XL Moller NP Olefsky JM Lawrence DS Zhang ZY 《Biochemistry》2003,42(44):12792-12804
130.
Roland Hischier Martin Baitz Rolf Bretz Rolf Frischknecht Niels Jungbluth Torsten Marheineke Phil McKeown Michiel Oele Philippe Osset Isa Renner Tim Skone Helena Wessman Angeline S. H. de Beaufort 《The International Journal of Life Cycle Assessment》2001,6(4):192-198
Data availability and data quality are still critical factors for successful LCA work. The SETAC-Europe LCA Working Group
‘Data Availability and Data Quality’ has therefore focused on ongoing developments toward a common data exchange format, public
databases and accepted quality measures to find science-based solutions than can be widely accepted. A necessary prerequisite
for the free flow and exchange of life cycle inventory (LCI) data and the comparability of LCIs is the consistent definition,
nomenclature, and use of inventory parameters. This is the main subject of the subgroup ‘Recommended List of Exchanges’ that
presents its results and findings here:
相似文献
• | Rigid parameter lists for LCIs are not practical; especially, compulsory lists of measurements for all inventories are counterproductive. Instead, practitioners should be obliged to give the rationale for their scientific choice of selected and omitted parameters. The standardized (not: mandatory!) parameter list established by the subgroup can help to facilitate this. |
• | The standardized nomenclature of LCI parameters and the standardized list of measurement bases (units) for these parameters need not be appliedinternally (e.g. in LCA software), but should be adhered to inexternal communications (data for publication and exchange). Deviations need to be clearly stated. |
• | Sum parameters may or may not overlap - misinterpretations in either direction introduce a bias of unknown significance in the subsequent life cycle impact assessments (LCIA). The only person who can discriminate unambiguously is the practitioner who measures or calculates such values. Therefore, a clear statement of independence or overlap is necessary for every sum parameter reported. |
• | Sum parameters should be only used when the group of emissions as such is measured. Individually measured emission parameters should not be hidden in group or sum parameters. |
• | Problematic substances (such as carcinogens, ozone depleting agents and the like) maynever be obscured in group emissions (together with less harmful substances or with substances of different environmental impact), butmust be determined and reported individually, as mentioned in paragraph 3.3 of this article. |
• | Mass and energy balances should be carried out on a unit process level. Mass balances should be done on the level of the entire mass flow in a process as well as on the level of individual chemical elements. |
• | Whenever possible, practitioners should try to fill data gaps with their knowledge of analogous processes, environmental expert judgements, mass balance calculations, worst case assumptions or similar estimation procedures. |