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1.
Thioredoxin and glutathione systems are the major thiol-dependent redox systems in animal cells. They transfer via the reversible oxidoreduction of thiols the reducing equivalents of NADPH to numerous substrates and substrate reductases and constitute major defenses against oxidative stress. In this study, we cloned from the helminth parasite Echinococcus granulosus two trans-spliced mRNA variants that encode thioredoxin glutathione reductases (TGR). These variants code for mitochondrial and cytosolic selenocysteine-containing isoforms that possess identical glutaredoxin (Grx) and thioredoxin reductase (TR) domains and differ exclusively in their N termini. Western blot analysis of subcellular fractions with specific anti-TGR antibodies showed that TGR is present in both compartments. The biochemical characterization of the native purified TGR suggests that the Grx and TR domains of the enzyme can function either coupled or independently of each other, because the Grx domain can accept electrons from either TR domains or the glutathione system and the TR domains can transfer electrons to either the fused Grx domain or to E. granulosus thioredoxin.  相似文献   
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Introduction

We have previously reported that bacterial toxins, especially endotoxins such as lipopolysaccharides (LPS), might be important causative agents in the pathogenesis of rheumatoid arthritis (RA) in an in vitro model that simulates the potential effects of residing in damp buildings. Since numerous inflammatory processes are linked with the nuclear factor-κB (NF-κB), we investigated in detail the effects of LPS on the NF-κB pathway and the postulated formation of procollagen-endotoxin complexes.

Methods

An in vitro model of human chondrocytes was used to investigate LPS-mediated inflammatory signaling.

Results

Immunoelectron microscopy revealed that LPS physically interact with collagen type II in the extracellular matrix (ECM) and anti-collagen type II significantly reduced this interaction. BMS-345541 (a specific inhibitor of IκB kinase (IKK)) or wortmannin (a specific inhibitor of phosphatidylinositol 3-kinase (PI-3K)) inhibited the LPS-induced degradation of the ECM and apoptosis in chondrocytes. This effect was completely inhibited by combining BMS-345541 and wortmannin. Furthermore, BMS-345541 and/or wortmannin suppressed the LPS-induced upregulation of catabolic enzymes that mediate ECM degradation (matrix metalloproteinases-9, -13), cyclooxygenase-2 and apoptosis (activated caspase-3). These proteins are regulated by NF-κB, suggesting that the NF-κB and PI-3K pathways are involved in LPS-induced cartilage degradation. The induction of NF-κB correlated with activation of IκBα kinase, IκBα phosphorylation, IκBα degradation, p65 phosphorylation and p65 nuclear translocation. Further upstream, LPS induced the expression of Toll-like receptor 4 (TLR4) and bound with TLR4, indicating that LPS acts through TLR4.

Conclusion

These results suggest that molecular associations between LPS/TLR4/collagen type II in chondrocytes upregulate the NF-κB and PI-3K signaling pathways and activate proinflammatory activity.  相似文献   
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Summary PhoE protein of Escherichia coli K12 is an outer membrane protein which is supposed to span the membrane sixteen times. By creating a deletion which removes the last membrane-spanning fragment and studying the localization of the truncated PhoE, we show that this fragment is indispensable for trimerization and outer membrane localization. In addition, circumstantial evidence for the proposed topology model of the protein was obtained. An insertion mutation in a region supposed to be cell surface-exposed, interferes with the binding of a monoclonal antibody which recognizes a cell surface-exposed epitope of the protein.  相似文献   
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Summary The functional morphology of the neuroendocrine system producing sodium influx-stimulating (SIS) peptide in the pond snail, Lymnaea stagnalis, was studied by in situ hybridization and immunocytochemistry. The SIS-peptide, which is 76 amino acids long, stimulates sodium uptake from the ambient medium. Two synthetic DNA probes were used for in situ hybridization. The nucleotide sequences were chosen from the cDNA structure; they encode amino acids 8–17 and 64–73, respectively. SIS-peptide sequences 10–20 and 67–76 were synthesized and antibodies were raised to them and affinity-purified. In addition to these antibodies, a monoclonal antibody raised to a bioactive, high-pressure liquid chromatography (HPLC)-purified brain extract was used for immunocytochemistry. Paraffin sections of central nervous systems and of whole snails were studied. The SIS-peptide system could be identified as the previously described yellow cell (YC) system by comparing alternate sections treated with the DNA probes, stained with the antibodies, or stained with alcian blue-alcian yellow. SIS-peptide neurons (45) occur in the ganglia of the visceral ring and in the proximal parts of visceral nerves. Axons run in the nerves of these and in several nerves of other ganglia. Numerous axon branches penetrate the perineurium forming a vast central neurohemal area. The SIS-peptide system innervates the pericardium, the nephridial gland, the reno-pericardial canal, the ureter, the spermoviduct and gonadal acini, the anterior aorta, the ventral buccal artery, and the penis protractor muscle. The morphology of the system is discussed in relation to the process of sodium ion uptake from the ambient medium and from pro-urine, and to that of regulating blood pressure. In the central nervous system and other organs, neurons and axons not labeled with the DNA probes, but immunoreactive to one or two of the antibodies, were observed. It seems unlikely that these elements are functionally related to the SIS-peptide system.  相似文献   
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For a given level of adiposity, greater lower body circumferences appear to exert a protective effect on several disease outcomes including cardiovascular disease and diabetes; however, the independent associations between extremity circumferences and mortality have not been widely investigated. The purpose of this study was to determine the independent and shared influences of upper- and lower-body circumferences on the risk of mortality in a population-based sample of adults. The sample included 10,638 adults 20-69 years of age (5,012 men; 5,626 women) from the nationally representative 1981 Canada Fitness Survey (CFS), who were monitored for over 12 years for mortality. BMI was calculated from measured height and weight. Waist, hip, thigh, calf, and upper arm circumferences were measured using a flexible, nonelastic anthropometric tape. Sex-specific proportional hazards regression models were used to evaluate the relationship between standardized values (Z-scores) of extremity circumference measures, waist circumference (WC) and mortality. Age, smoking status, alcohol consumption, and leisure-time physical activity were collected by questionnaire and were included as covariates. During 131,563 person-years of follow-up, there were 340 deaths in men and 231 in women. After mutual adjustment, WC was positively associated with mortality whereas arm, thigh, and calf circumferences were significantly protective in men, and arm and thigh circumferences were protective in women. In conclusion, waist and extremity circumferences appear to have opposite, independent effects on mortality in this sample of Canadians. Independent of BMI and WC, men and women with larger extremity circumferences had a lower risk of mortality.  相似文献   
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Objective: To prospectively evaluate whether childbearing leads to development of overweight in women and to evaluate the role of other known risk factors. Research Methods and Procedures: A prospective, multicenter observational study, the Coronary Artery Risk Development in Young Adults (CARDIA) Study from 1986 to 1996, examined subjects at baseline and in follow‐up years 2, 5, 7, and 10. Included were 998 (328 black and 670 white) nulliparous women, age 18‐30 years, who were not overweight at baseline. Relative odds for incident overweight (BMI ≥ 25 kg/m2) associated with parity change (0, 1, or 2+) and risk factors were estimated using discrete‐time survival models adjusted for baseline and time‐dependent covariates. Results: Parity change‐association with development of overweight depended on smoking habit (interaction, p < 0.001). In multivariate adjusted models, 1 and 2+ births vs. 0, respectively, were associated with increased risk for development of overweight among never smokers [odds ratio (OR) = 2.66; 95% confidence interval (CI): 1.80, 3.93, and 2.10, 95% CI: 1.24, 3.56] and decreased risk among current smokers (OR = 0.41; 95% CI: 0.17, 0.96, and 0.36, 95% CI: 0.08, 1.65). Risk was increased for black vs. white race (OR = 3.49; 95% CI: 2.59, 4.69), frequent weight cycling (OR = 1.45; 95% CI: 1.03, 2.04), and high school education or less (OR = 2.21; 95% CI: 1.50, 3.26) and was decreased for highest physical activity quartile (OR = 0.62; 95% CI: 0.43, 0.90). Discussion: Childbearing contributes to development of overweight in nonsmokers but not in smokers, where development of overweight is less likely in women who bear children. Race, education, and behaviors are important factors in development of overweight in young women.  相似文献   
9.
  总被引:1,自引:0,他引:1  
One hundred and eighty five samples of red, white and rosé wines and different juices purchased in Entre Rios, Argentina, were analyzed for the Alternaria mycotoxins alternariol (AOH) and alternariol methyl ether (AME). White wines were analyzed after removal of alcohol by a nitrogen stream and concentrated. AOH in red wines was cleaned up by solid-phase extraction columns in series (octadecyl and amino propyl modified silica) and AME quantified directly on the sample. The juices were filtered and concentrated, and then all sample extracts were quantified by high performance liquid chromatography with photodiode array detector that allows confirmation through UV spectra. Method validation revealed a good sensitivity with adequate LOD and LOQ for AME and less sensitivity for AOH (i.e. white wine: AME 0.8 and 1.4 ng/mL, AOH 2 and 3.3 ng/mL; red wine: AME 0.1 and 0.2 ng/mL, AOH 4.5 and 7.5 ng/mL; apple juice: AME 1.7 and 2.8 ng/mL, AOH 5 and 9 ng/mL; other juices: AME 2.0 and 3.1 ng/mL, AOH 6 and 10 ng/mL). Recoveries in all cases were greater than 80 %. Four of 53 white wine samples were contaminated with AOH with a maximum level of 18 ng/mL, 6 of 56 samples of red wine had a maximum of 13 ng/mL, and 3 of 68 samples of juices had traces of AOH. AME was less frequently detected than AOH, and the LOD and LOQ for AME are smaller than for AOH. Only three samples of white wine and one of red wine were contaminated, but in only one white wine sample (AME 225 ng/mL) did the toxin level exceed the LOQ.  相似文献   
10.
Asymmetric osteoarthritis (OA) is a common type of OA in the ankle joint. OA also influences the muscles surrounding a joint, however, little is known about the muscle activation in asymmetric ankle OA. Therefore, the aim of this study was to characterize the patients’ muscle activation during isometric ankle torque measurements and level walking. Surface electromyography (EMG) was measured of gastrocnemius medialis (GM) and lateralis (GL), soleus (SO), tibialis anterior (TA), and peroneus longus (PL) in 12 healthy subjects and 12 ankle OA patients. To obtain time and frequency components of the EMG power a wavelet transformation was performed. Furthermore, entropy was introduced to characterize the homogeneity of the wavelet patterns.Patients produced lower plantar- and dorsiflexion torques and their TA wavelet spectrum was shifted towards lower frequencies. While walking, the patients’ muscles were active with a lower intensity and over a broader time–frequency region. In contrast to controls and varus OA patients, maximal GM activity of valgus OA patients lagged behind the activity of GL and SO. In both tasks, PL of the valgus patients contained more low frequency power. The results of this study will help to assess whether surgical interventions of ankle OA can reestablish the muscle activation patterns.  相似文献   
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