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61.
Overexpression of MMP9 in macrophages attenuates pulmonary fibrosis induced by bleomycin 总被引:1,自引:0,他引:1
Cabrera S Gaxiola M Arreola JL Ramírez R Jara P D'Armiento J Richards T Selman M Pardo A 《The international journal of biochemistry & cell biology》2007,39(12):2324-2338
Pulmonary fibrosis is a common response to a variety of lung injuries, characterized by fibroblast/myofibroblast expansion and abnormal accumulation of extracellular matrix. An increased expression of matrix metalloprotease 9 (MMP9) in human and experimental lung fibrosis has been documented, but its role in the fibrotic response is unclear. We studied the effect of MMP9 overexpression in bleomycin-driven lung fibrosis using transgenic mice expressing human MMP9 in alveolar macrophages (hMMP9-TG). At 8 weeks post-bleomycin, the extent of fibrotic lesions and OH-proline content were significantly decreased in the TG mice compared to the WT mice. The decreased fibrosis in hMMP9-TG mice was preceded by a significant reduction of neutrophils and lymphocytes in bronchoalveolar lavage (BAL) at 1 and 4 weeks post-bleomycin, respectively, as well as by significantly less TIMP-1 than the WT mice. From a variety of cytokines/chemokines investigated, we found that BAL levels of insulin-like growth factor binding protein-3 (IGFBP3) as well as the immunoreactive protein in the lungs were significantly lower in hMMP9-TG mice compared with WT mice despite similar levels of gene expression. Using IGFBP-3 substrate zymography we found that BAL from TG mice at 1 week after bleomycin cleaved IGFBP-3. Further, we demonstrated that MMP9 degraded IGFBP-3 into lower molecular mass fragments. These findings suggest that increased activity of MMP9 secreted by alveolar macrophages in the lung microenvironment may have an antifibrotic effect and provide a potential mechanism involving IGFBP3 degradation. 相似文献
62.
Marcelo De Franco Patrícia dos Santos Carneiro Luciana Carla Peters Francisca Vorraro Andrea Borrego Orlando Garcia Ribeiro Nancy Starobinas Wafa Koury Cabrera Olga Martinez Ibañez 《Mammalian genome》2007,18(4):263-269
Lines of mice were obtained by selective breeding for maximum (AIRmax) or minimum (AIRmin) acute inflammation. They present
distinct neutrophil influx and show frequency disequilibrium of the solute carrier family 11a member 1
(Slc11a1) alleles. This gene is involved in ion transport at the endosomes within macrophages and neutrophils, interfering in their
activation. Homozygous AIRmax and AIRmin sublines for the Slc11a1 gene were produced to examine the interaction of this gene with the acute inflammatory loci. The present work investigated
wound-healing traits in AIRmax and AIRmin mice, in F1 and F2 intercrosses, and in Slc11a1 sublines. Two-millimeter ear punches were made in the mice and hole closure was measured during 40 days. AIRmax mice demonstrated
significant tissue repair while AIRmin mice did not. Significant differences between the responses of male and female mice
were also observed. Wound-healing traits demonstrated a correlation with neutrophil influx in F2 populations. AIRmax
SS
showed higher ear-wound closure than AIRmax
RR
mice, suggesting that the Slc11a1
S allele favored ear tissue repair. QTL analysis has detected two inflammatory loci modulating ear wound healing on chromosomes
1 and 14. These results suggest the involvement of the acute inflammation modifier QTL in the wound-healing phenotype. 相似文献
63.
Huiping Zhu Robert M Cabrera Bogdan J Wlodarczyk Daniel Bozinov Deli Wang Robert J Schwartz Richard H Finnell 《BMC developmental biology》2007,7(1):128
Background
Heart anomalies are the most frequently observed among all human congenital defects. As with the situation for neural tube defects (NTDs), it has been demonstrated that women who use multivitamins containing folic acid peri-conceptionally have a reduced risk for delivering offspring with conotruncal heart defects [1–3]. Cellular folate transport is mediated by a receptor or binding protein and by an anionic transporter protein system. Defective function of the Folr1 (also known as Folbp1; homologue of human FRα) gene in mice results in inadequate transport, accumulation, or metabolism of folate during cardiovascular morphogenesis. 相似文献64.
Cruces-Ángeles ME Cabrera N Pérez-Montfort R Reyes-López CA Hernández-Arana A 《Protein and peptide letters》2011,18(12):1290-1298
Several variants of Saccharomyces cerevisiae triosephosphate isomerase (yTIM) were studied to determine how mutations of conserved and non-conserved Cys residues affect the enzyme. Wild-type yTIM has two buried free cysteines: Cys 41 (non-conserved) and the invariant Cys 126. Single-site mutants, containing substitutions of these cysteines with Ala, Val, or Ser (the three most conservative changes for a buried Cys, according to substitution matrices), were examined for stability and enzymatic activity. Neither of the Cys residues was found to be essential for enzyme catalysis. Determination of the global stability of the mutants indicated that, regardless of which Cys was substituted, individual Cys→Ala and Cys→Val mutations, as well as the C41S substitution, all decrease the unfolding free energy of the dimeric protein by less than 23 kJ mol(-1) (at 37 °C, pH 7.4), as compared to the wild-type enzyme. In contrast, a substantially larger destabilization (37 kJ mol(-1)) was found in the C126S mutant. These results suggest that, with the exception of C126S, all of these mutations can be regarded as neutral (i.e., mutations that do not impair the reproductive success of the organism). Accordingly, Cys 126 has remained invariant across evolution because its neutral substitutions by Ala or Val would require a highly unlikely, concerted double mutation at any of the Cys codons. Furthermore, detrimental effects to a cell expressing the C126S TIM mutant more likely arise from the high unfolding rate of this enzyme. 相似文献
65.
L.R. Comini I.M. Fernandez N.B. Rumie VittarS.C. Núñez Montoya J.L. Cabrera V.A. Rivarola 《Phytomedicine》2011,18(12):1093-1095
Searching for agents that could be effective in the treatment of cancer, special highlight has focused on the study of numerous plant-derived compounds. We previously demonstrated that anthraquinones (AQs) isolated from a vegetal species: Heterophyllaea pustulata Hook f. (Rubiaceae), such as rubiadin, rubiadin-1-methyl ether, soranjidiol, soranjidiol-1-methyl ether exhibit photosensitizing properties without antecedents as photodynamic agents in malignant cells. In the present study, we investigated the potential role of these AQs as a phototoxic agent against human breast carcinoma using MCF-7c3 cells. All AQs exhibited significant photocytotoxicity on cancer cells at the concentration of 100 μM with 1 J/cm2 light dose, resulting soranjidiol-1-methyl ether in complete cell destruction. The observed cellular killing by photoactivated AQs exhibited close relation with singlet oxygen production, except for soranjidiol-1-methyl ether, where cell viability decrease is in relation to uptake by tumor cells. 相似文献
66.
Triguero A Cabrera G Rodríguez M Soto J Zamora Y Pérez M Wormald MR Cremata JA 《Plant biotechnology journal》2011,9(9):1120-1130
Plant cells are able to perform most of the post-translational modifications that are required by recombinant proteins to achieve adequate bioactivity and pharmacokinetics. However, regarding N-glycosylation the processing of plant N-glycans in the Golgi apparatus displays major differences when compared with that of mammalian cells. These differences in N-glycosylation are expected to influence serum clearance rate of plant-derived monoclonal antibodies. The monoclonal antibody against the hepatitis B virus surface antigen expressed in Nicotiana tabacum leaves without KDEL endoplasmic reticulum (ER) retention signal (CB.Hep1(-)KDEL) and with a KDEL (Lys-Asp-Glu-Leu) fused to both IgG light and heavy chains (CB.Hep1(+)KDEL) were tested for in vivo stability in mice. Full characterization of N-glycosylation and aggregate formation in each monoclonal antibody batch was determined. The mouse counterpart (CB.Hep1) was used as control. Both (CB.Hep1(-)KDEL) and (CB.Hep1(+)KDEL) showed a faster initial clearance rate (first 24 h) compared with the analogous murine antibody while the terminal phase was similar in the three antibodies. Despite the differences between CB.Hep1(+)KDEL and CB.Hep1(-)KDEL N-glycans, the in vivo elimination in mice was indistinguishable from each other and higher than the murine monoclonal antibody. Molecular modelling confirmed that N-glycans linked to plantibodies were oriented away from the interdomain region, increasing the accessibility of the potential glycan epitopes by glycoprotein receptors that might be responsible for the difference in stability of these molecules. 相似文献
67.
García-Torres I Cabrera N Torres-Larios A Rodríguez-Bolaños M Díaz-Mazariegos S Gómez-Puyou A Perez-Montfort R 《PloS one》2011,6(4):e18791
For a better comprehension of the structure-function relationship in proteins it is necessary to identify the amino acids that are relevant for measurable protein functions. Because of the numerous contacts that amino acids establish within proteins and the cooperative nature of their interactions, it is difficult to achieve this goal. Thus, the study of protein-ligand interactions is usually focused on local environmental structural differences. Here, using a pair of triosephosphate isomerase enzymes with extremely high homology from two different organisms, we demonstrate that the control of a seventy-fold difference in reactivity of the interface cysteine is located in several amino acids from two structurally unrelated regions that do not contact the cysteine sensitive to the sulfhydryl reagent methylmethane sulfonate, nor the residues in its immediate vicinity. The change in reactivity is due to an increase in the apparent pKa of the interface cysteine produced by the mutated residues. Our work, which involved grafting systematically portions of one protein into the other protein, revealed unsuspected and multisite long-range interactions that modulate the properties of the interface cysteines and has general implications for future studies on protein structure-function relationships. 相似文献
68.
69.
Cózar JM Canton J Tallada M Concha A Cabrera T Garrido F Ruiz-Cabello Osuna F 《Cancer immunology, immunotherapy : CII》2005,54(9):858-866
Recent data suggest that chemokines and chemokine receptors mediate leukocyte recruitment of all components of the antitumor response. This study aimed to phenotypically characterize the immune lymphocyte infiltrate in human renal cell carcinomas (RCCs) and at the invasive margin (tumor–host interface) and to define the association of these findings with established prognostic indicators. Tumor infiltrating lymphocytes (TILs) were obtained from 24 patients with RCC undergoing radical nephrectomy. Peripheral blood cells from 37 patients were also obtained before surgery. Our findings are consistent with the preferential recruitment of CD4+ Th1-polarized effector memory cells that express CXCR3/CCR5. These cells were the main component of TILs and expressed as CXCR3, CCR5, CD45RO, and CD95. Natural killer (NK) cells were found in significantly higher proportions in TILs of RCCs than in peripheral blood lymphocytes (PBLs) or in other tumors studied (colorectal and breast cancers), where these cells were found in small proportions. No differences in nuclear grade or other studied parameters were observed between the TILs and the lymphocytes present at the invasive margin, which showed a similar composition. However, differences were found according to the tumor stage. First, significantly fewer NK cells were observed in PBLs from metastatic patients. Second, a significantly lower proportion of CCR5/CXCR3/CD4+ cells and a higher proportion of CCR4/CD4+ cells were observed in metastatic patients, suggesting that preferential Th1-polarization may gradually change during the progression of renal cancer cells. Finally, the frequency of CD25/CD4+ cells was higher in metastatic patients. Although the sample of patients with metastasis was small, the overall results suggest a change in composition of the TILs that may potentially confer a selective advantage for tumor growth and may account for the suppression of an effective cytotoxic response. 相似文献
70.
Cobo F Stacey GN Hunt C Cabrera C Nieto A Montes R Cortés JL Catalina P Barnie A Concha A 《Applied microbiology and biotechnology》2005,68(4):456-466
The transplant of cells of human origin is an increasingly complex sector of medicine which entails great opportunities for
the treatment of a range of diseases. Stem cell banks should assure the quality, traceability and safety of cultures for transplantation
and must implement an effective programme to prevent contamination of the final product. In donors, the presence of infectious
micro-organisms, like human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T cell lymphotrophic virus,
should be evaluated in addition to the possibility of other new infectious agents (e.g. transmissible spongiform encephalopathies
and severe acute respiratory syndrome). The introduction of the nucleic acid amplification can avoid the window period of
these viral infections. Contamination from the laboratory environment can be achieved by routine screening for bacteria, fungi,
yeast and mycoplasma by European pharmacopoeia tests. Fastidious micro-organisms, and an adventitious or endogenous virus,
is a well-known fact that will also have to be considered for processes involving in vitro culture of stem cells. It is also
a standard part of current good practice in stem cell banks to carry out routine environmental microbiological monitoring
of the cleanrooms where the cell cultures and their products are prepared. The risk of viral contamination from products of
animal origin, like bovine serum and mouse fibroblasts as a “feeder layer” for the development of embryonic cell lines, should
also be considered. Stem cell lines should be tested for prion particles and a virus of animal origin that assure an acceptable
quality. 相似文献