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911.
912.
Interferon-gamma (IFNG) induces apoptotic cell death in bovine luteal cells, but the pathway(s) involved in this process are not well defined. Evidence supporting the involvement of an IFNG-inducible enzymatic pathway that degrades tryptophan in IFNG-induced death of bovine luteal cells is presented in this study. The IFNG-inducible enzyme indoleamine 2,3-dioxygenase (INDO) catalyzes the first step in a metabolic pathway that degrades tryptophan. In the first experiment, RT-PCR revealed the presence of INDO mRNA in luteal cells treated with IFNG, but not in untreated cells. To determine whether INDO participates in IFNG-induced death of bovine luteal cells, an experiment was performed to test the effect of 1-methyl-D-tryptophan (1-MT), an inhibitor of INDO, on IFNG-induced DNA fragmentation in luteal cells. Single-cell gel electrophoresis and microscopic image analysis revealed that 1-MT inhibited DNA fragmentation induced by IFNG. To determine whether supplementation of cell cultures with additional tryptophan could also protect luteal cells from IFNG-induced DNA fragmentation, luteal cells were cultured in the presence of IFNG, and L-tryptophan was added to cultures to achieve final concentrations that were 5-, 10-, or 25-fold higher than the concentration of L-tryptophan found in nonsupplemented culture medium. Supplementation of IFNG-treated luteal cell cultures with elevated concentrations of tryptophan also prevented IFNG-induced DNA fragmentation. We conclude that INDO participates in IFNG-induced death of bovine luteal cells, through a mechanism that involves degradation of tryptophan, thereby reducing tryptophan concentrations to a point insufficient to meet luteal cells needs. 相似文献
913.
Circular dichroism and resolution-enhanced Fourier transform infrared reveal induction of secondary structural elements on peptidyl-prolyl cis–trans isomerase A (PpiA) from Mycobacterium tuberculosis upon binding cyclosporin A (CsA). Thermal denaturation shows aggregation of PpiA at higher temperatures (>70 °C) and CsA fails to impart stabilization in protein structure. However, CsA stabilizes PpiA structure in urea denaturation. In presence/absence of CsA, urea-induced reversible unfolding of secondary and tertiary structures follows two-state and three-state transition, respectively. The chemical unfolding results also demonstrate that loss in the tertiary structure precedes the loss in secondary structure both in presence and absence of CsA at the initial stages. Fluorescence quenching suggests presence of a positive barrier around tryptophan microenvironment of PpiA. 相似文献
914.
Uteroglobin (UG) is an anti-inflammatory protein secreted by the airway epithelia of all mammals. UG-knockout (UG-KO) mice sporadically develop focal pulmonary fibrosis (PF), a group of complex interstitial disorders of the lung that has high mortality and morbidity; however, the molecular mechanism(s) remains unclear. We report here that UG-KO mice are extraordinarily sensitive to bleomycin, an anti-cancer agent known to induce PF and readily develop PF when treated with an extremely low dose of bleomycin that has virtually no effect on the wild type littermates. We further demonstrate that UG prevents PF suppressing bleomycin-induced production of pro-inflammatory T-helper 2 cytokines and TGF-beta, which are also pro-fibrotic. Our results define a critical role of UG in preventing the development of PF and provide the proof of principle that recombinant UG may have therapeutic potential. 相似文献
915.
Choudhury NR Malik PS Singh DK Islam MN Kaliappan K Mukherjee SK 《Nucleic acids research》2006,34(21):6362-6377
Geminiviruses replicate by rolling circle mode of replication (RCR) and the viral Rep protein initiates RCR by the site-specific nicking at a conserved nonamer (TAATATT downward arrow AC) sequence. The mechanism of subsequent steps of the replication process, e.g. helicase activity to drive fork-elongation, etc. has largely remained obscure. Here we show that Rep of a geminivirus, namely, Mungbean yellow mosaic India virus (MYMIV), acts as a replicative helicase. The Rep-helicase, requiring > or =6 nt space for its efficient activity, translocates in the 3'-->5' direction, and the presence of forked junction in the substrate does not influence the activity to any great extent. Rep forms a large oligomeric complex and the helicase activity is dependent on the oligomeric conformation ( approximately 24mer). The role of Rep as a replicative helicase has been demonstrated through ex vivo studies in Saccharomyces cerevisiae and in planta analyses in Nicotiana tabacum. We also establish that such helicase activity is not confined to the MYMIV system alone, but is also true with at least two other begomoviruses, viz., Mungbean yellow mosaic virus (MYMV) and Indian cassava mosaic virus (ICMV). 相似文献
916.
The paper considers the problem of determining the number of matched sets in 1 : M matched case-control studies with a categorical exposure having k + 1 categories, k > or = 1. The basic interest lies in constructing a test statistic to test whether the exposure is associated with the disease. Estimates of the k odds ratios for 1 : M matched case-control studies with dichotomous exposure and for 1 : 1 matched case-control studies with exposure at several levels are presented in Breslow and Day (1980), but results holding in full generality were not available so far. We propose a score test for testing the hypothesis of no association between disease and the polychotomous exposure. We exploit the power function of this test statistic to calculate the required number of matched sets to detect specific departures from the null hypothesis of no association. We also consider the situation when there is a natural ordering among the levels of the exposure variable. For ordinal exposure variables, we propose a test for detecting trend in disease risk with increasing levels of the exposure variable. Our methods are illustrated with two datasets, one is a real dataset on colorectal cancer in rats and the other a simulated dataset for studying disease-gene association. 相似文献
917.
Yeast Nhx1 [Na+(K+)/H+ exchanger 1] is an intracellular Na+(K+)/H+ exchanger, localizing to the late endosome where it is important for ion homoeostasis and vesicle trafficking. Phylogenetic analysis of NHE (Na+/H+ exchanger) sequences has identified orthologous proteins, including HsNHE6 (human NHE6), HsNHE7 and HsNHE9 of unknown physiological role. These appear distinct from well-studied mammalian plasma membrane isoforms (NHE1-NHE5). To explore the differences between plasma membrane and intracellular NHEs and understand the link between ion homoeostasis and vesicle trafficking, we examined the consequence of replacing residues in the intramembranous H10 loop of Nhx1 between transmembrane segments 9 and 10. The critical role for the carboxy group of Glu355 in ion transport is consistent with the invariance of this residue in all NHEs. Surprisingly, residues specifically conserved in the intracellular isoforms (such as Phe357 and Tyr361) could not be replaced with closely similar residues (leucine and phenylalanine) found in the plasma membrane isoforms without loss of function, revealing unexpected side chain specificity. The trafficking phenotypes of all Nhx1 mutants, including hygromycin-sensitivity and missorting of carboxypeptidase Y, were found to directly correlate with pH homoeostasis defects and could be proportionately corrected by titration with weak base. The present study demonstrates the importance of the H10 loop of the NHE family, highlights the differences between plasma membrane and intracellular isoforms and shows that trafficking defects are tightly coupled with pH homoeostasis. 相似文献
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920.