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31.
Viganò A Vasso M Caretti A Bravatà V Terraneo L Fania C Capitanio D Samaja M Gelfi C 《Proteomics》2011,11(21):4202-4217
Exploring cellular mechanisms underlying beneficial and detrimental responses to hypoxia represents the object of the present study. Signaling molecules controlling adaptation to hypoxia (HIF-1α), energy balance (AMPK), mitochondrial biogenesis (PGC-1α), autophagic/apoptotic processes regulation and proteomic dysregulation were assessed. Responses to acute hypoxia (AH) and chronic hypoxia (CH) in mouse heart proteome were detected by 2-D DIGE, mass spectrometry and antigen-antibody reactions. Both in AH and CH, the results indicated a deregulation of proteins related to sarcomere stabilization and muscle contraction. Neither in AH nor in CH the HIF-1α stabilization was observed. In AH, the metabolic adaptation to lack of oxygen was controlled by AMPK activation and sustained by an up-regulation of adenosylhomocysteinase and acetyl-CoA synthetase. AH was characterized by the mitophagic protein Bnip 3 increment. PGC-1α, a master regulator of mitochondrial biogenesis, was down-regulated. CH was characterized by the up-regulation of enzymes involved in antioxidant defense, in aldehyde bio-product detoxification and in misfolded protein degradation. In addition, a general down-regulation of enzymes controlling anaerobic metabolism was observed. After 10 days of hypoxia, cardioprotective molecules were substantially decreased whereas pro-apoptotic molecules increased accompained by down-regulation of specific target proteins. 相似文献
32.
Freire RS Morais SM Catunda-Junior FE Pinheiro DC 《Bioorganic & medicinal chemistry》2005,13(13):4353-4358
Some derivatives of trans-anethole [1-methoxy-4-(1-propenyl)-benzene] (1) were synthesized, by introducing hydroxyl groups in the double bond of the propenyl moiety. Two types of reactions were performed: (i) oxymercuration/demercuration that formed two products, the mono-hydroxyl derivative, 1-hydroxy-1-(4-methoxyphenyl)-propane (2) and in lesser extent the dihydroxyl derivative, 1,2-dihydroxy-1-(4-methoxyphenyl)-propane (3) and (ii) epoxidation with m-chloroperbenzoic acid that also led to the formation of two products, the dihydroxyl derivative (3) and the correspondent m-chloro-benzoic acid mono-ester, 1-hydroxy-1(4-methoxyphenyl)-2-m-chlorobenzoyl-propane (4). The structures of these compounds were confirmed mainly by mass, IR, 1H and 13C NMR spectral data. The activity of anethole and hydroxylated derivatives was evaluated using antioxidant, anti-inflammatory and gastroprotector tests. Compounds (2) and (3) were more active antioxidant agents than (1) and (4). In the anti-inflammatory assay, anethole showed lower activity than hydroxylated derivatives. Anethole and in lesser extent its derivatives 2 and 4 showed significant gastroprotector activity. All tested compounds do not alter significantly the total number of white blood cells. 相似文献
33.
Piccoli C Ria R Scrima R Cela O D'Aprile A Boffoli D Falzetti F Tabilio A Capitanio N 《The Journal of biological chemistry》2005,280(28):26467-26476
34.
Celegato B Capitanio D Pescatori M Romualdi C Pacchioni B Cagnin S Viganò A Colantoni L Begum S Ricci E Wait R Lanfranchi G Gelfi C 《Proteomics》2006,6(19):5303-5321
35.
Capitanio JP Kyes RC Fairbanks LA 《ILAR journal / National Research Council, Institute of Laboratory Animal Resources》2006,47(4):294-306
Nonhuman primates from domestic sources constitute an important resource for the research community. The life history of the Old World monkey species that comprise the bulk of this resource is described, and issues that colony managers and researchers alike should consider regarding animal selection (e.g., species, age, sex, rearing history, temperament, genotype, viral status, geographic origin) are discussed. Preparation of domestically bred animals for research usually involves some combination of social separation, relocation, resocialization, alterations in physical space, photoperiod, and diet, as well as exposure to novel environments. The research literature that has focused on these issues is reviewed, and authors suggest that once animals have been assigned to their project housing situation, a period ranging up to 3 mo (depending on the magnitude of the change in housing) might be warranted before an experimental protocol should begin. Attention to issues of animal selection and conditioning by both researchers and colony managers can lead to the shared goal of high-quality research that utilizes the minimal number of animals. 相似文献
36.
The crystallographic structures of functional fragments of ErbBs have provided excellent insights into the geometry of growth factor binding and receptor dimerization. By placing together receptor fragments to build structural models of entire receptors, we expect to understand how these enzymes are allosterically regulated; however, several predictions from these models are inconsistent with experimental evidence from cells. The opening of this gap underlines the need to investigate intact ErbBs by combining cellular and structural studies into a full picture. 相似文献
37.
Du L Zhao G Lin Y Sui H Chan C Ma S He Y Jiang S Wu C Yuen KY Jin DY Zhou Y Zheng BJ 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(2):948-956
We have previously reported that a subunit protein vaccine based on the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus (SARS-CoV) spike protein and a recombinant adeno-associated virus (rAAV)-based RBD (RBD-rAAV) vaccine could induce highly potent neutralizing Ab responses in immunized animals. In this study, systemic, mucosal, and cellular immune responses and long-term protective immunity induced by RBD-rAAV were further characterized in a BALB/c mouse model, with comparison of the i.m. and intranasal (i.n.) routes of administration. Our results demonstrated that: 1) the i.n. vaccination induced a systemic humoral immune response of comparable strength and shorter duration than the i.m. vaccination, but the local humoral immune response was much stronger; 2) the i.n. vaccination elicited stronger systemic and local specific cytotoxic T cell responses than the i.m. vaccination, as evidenced by higher prevalence of IL-2 and/or IFN-gamma-producing CD3+/CD8+ T cells in both lungs and spleen; 3) the i.n. vaccination induced similar protection as the i.m. vaccination against SARS-CoV challenge in mice; 4) higher titers of mucosal IgA and serum-neutralizing Ab were associated with lower viral load and less pulmonary pathological damage, while no Ab-mediated disease enhancement effect was observed; and 5) the vaccination could provide long-term protection against SARS-CoV infection. Taken together, our findings suggest that RBD-rAAV can be further developed into a vaccine candidate for prevention of SARS and that i.n. vaccination may be the preferred route of administration due to its ability to induce SARS-CoV-specific systemic and mucosal immune responses and its better safety profile. 相似文献
38.
Nunez-Cruz S Yeo WC Rothman J Ojha P Bassiri H Juntilla M Davidson D Veillette A Koretzky GA Nichols KE 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(4):2311-2320
The adaptor molecule SAP (signaling lymphocytic activation molecule-associated protein) plays a critical role during NK T (NKT) cell development in humans and mice. In CD4(+) T cells, SAP interacts with the tyrosine kinase Fyn to deliver signals required for TCR-induced Th2-type cytokine production. To determine whether the SAP-dependent signals controlling NKT cell ontogeny rely on its binding to Fyn, we used the OP9-DL1 system to initiate structure function studies of SAP in murine NKT cell development. In cultures containing wild-type (WT) hematopoietic progenitors, we noted the transient emergence of cells that reacted with the NKT cell-specific agonist alpha-galactosyl ceramide and its analog PBS57. Sap(-/-) cells failed to give rise to NKT cells in vitro; however, their development could be rescued by re-expression of WT SAP. Emergence of NKT cells was also restored by a mutant version of SAP (SAP R78A) that cannot bind to Fyn, but with less efficiency than WT SAP. This finding was accentuated in vivo in Sap(R78A) knock-in mice as well as Sap(R78A) competitive bone marrow chimeras, which retained NKT cells but at significantly reduced numbers compared with controls. Unlike Sap(R78A) CD4(+) T cells, which produce reduced levels of IL-4 following TCR ligation, alpha-galactosyl ceramide-stimulated NKT cells from the livers and spleens of Sap(R78A) mice produced Th2 cytokines and activated NK cells in a manner mimicking WT cells. Thus, SAP appears to use differential signaling mechanisms in NKT cells, with optimal ontogeny requiring Fyn binding, while functional responses occur independently of this interaction. 相似文献
39.
40.
Mudge J Miller NA Khrebtukova I Lindquist IE May GD Huntley JJ Luo S Zhang L van Velkinburgh JC Farmer AD Lewis S Beavis WD Schilkey FD Virk SM Black CF Myers MK Mader LC Langley RJ Utsey JP Kim RW Roberts RC Khalsa SK Garcia M Ambriz-Griffith V Harlan R Czika W Martin S Wolfinger RD Perrone-Bizzozero NI Schroth GP Kingsmore SF 《PloS one》2008,3(11):e3625