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Franciele Martini Marlon Régis Leite Suzan Gonçalves Rosa Isabella Pregardier Klann Cristina Wayne Nogueira 《Cell biochemistry and function》2020,38(2):213-221
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has generated scientific interest because of its prevalence in the population. Studies indicate that physical exercise promotes neuroplasticity and improves cognitive function in animal models and in human beings. The aim of the present study was to investigate the effects of strength exercise on the hippocampal protein contents and memory performance in mice subjected to a model of sporadic AD induced by streptozotocin (STZ). Swiss mice received two injections of STZ (3 mg/kg, intracerebroventricular). After 21 days, they began physical training using a ladde. Mice performed this protocol for 4 weeks. After the last exercise training session, mice performed the Morris Water Maze test. The samples of hippocampus were excised and used to determine protein contents of brain-derived neurotrophic factor (BDNF), extracellular signal-regulated kinase-Ca2+ (ERK), calmodulin-dependent protein kinase (CAMKII) and cAMP-response element-binding protein (CREB) signalling pathway. Strength exercise was effective against the decrease in the time spent and distance travelled in the target quadrant by STZ-injected mice. Strength exercise was also effective against the reduction of mature BDNF, tropomyosin receptor kinase B and neuronal nuclear antigen (NeuN) hippocampal protein levels in STZ mice. The decrease in the hippocampal ratio of pERK/ERK, pCAMKII/CAMKII and pCREB/CREB induced by STZ was reversed by strength exercise. Strength exercise decreased Bax/Bcl2 ratio in the hippocampus of STZ-injected mice. The present study demonstrates that strength exercise modulated the hippocampal BDNF/ERK-CAMKII/CREB signalling pathway and suppressed STZ-induced spatial memory impairment in mice. 相似文献
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Robert B. Lochhead James F. Zachary Luciana Dalla Rosa Ying Ma John H. Weis Ryan M. O’Connell Janis J. Weis 《PloS one》2015,10(8)
MicroRNA-155 has been shown to play a role in immune activation and inflammation, and is suppressed by IL-10, an important anti-inflammatory cytokine. The established involvement of IL-10 in the murine model of Borrelia burgdorferi-induced Lyme arthritis and carditis allowed us to assess the interplay between IL-10 and miR-155 in vivo. As reported previously, Mir155 was highly upregulated in joints from infected severely arthritic B6 Il10-/- mice, but not in mildly arthritic B6 mice. In infected hearts, Mir155 was upregulated in both strains, suggesting a role of miR-155 in Lyme carditis. Using B. burgdorferi-infected B6, Mir155-/-, Il10-/-, and Mir155-/- Il10-/- double-knockout (DKO) mice, we found that anti-inflammatory IL-10 and pro-inflammatory miR-155 have opposite and somewhat compensatory effects on myeloid cell activity, cytokine production, and antibody response. Both IL-10 and miR-155 were required for suppression of Lyme carditis. Infected Mir155-/- mice developed moderate/severe carditis, had higher B. burgdorferi numbers, and had reduced Th1 cytokine expression in hearts. In contrast, while Il10-/- and DKO mice also developed severe carditis, hearts had reduced bacterial numbers and elevated Th1 and innate cytokine expression. Surprisingly, miR-155 had little effect on Lyme arthritis. These results show that antagonistic interplay between IL-10 and miR-155 is required to balance host defense and immune activation in vivo, and this balance is particularly important for suppression of Lyme carditis. These results also highlight tissue-specific differences in Lyme arthritis and carditis pathogenesis, and reveal the importance of IL-10-mediated regulation of miR-155 in maintaining healthy immunity. 相似文献
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L L Chen J J Rosa S Turner R B Pepinsky 《The Journal of biological chemistry》1991,266(27):18237-18243
We have developed a three-step cross-linking procedure that is specifically targeted at the carbohydrate on a protein and applied it to CD4 as a model system for studying the role of multivalent interactions in function. In the first step CD4 was oxidized with periodate, creating aldehydes that served as targets for the subsequent chemistry. Next the aldehydes were modified with cystamine, converting the reactive group into a thiol. Finally cross-linking through the thiol moiety was generated with the homobifunctional cross-linker bismaleimidohexane. With this procedure, approximately 60% of the CD4 was converted into higher molecular weight complexes that were soluble and retained function as assessed by glycoprotein gp120 binding activity. CD4 dimers and tetramers by mass were 4 and 15 times as active as CD4 monomer in blocking virus infection with HTLV-IIIB in an in vitro cellular assay. The cross-linking chemistry provides an efficient method for producing homomultimers of a glycoprotein. 相似文献
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D Prome Y Blouquit C Ponthus J C Prome J Rosa 《The Journal of biological chemistry》1991,266(20):13050-13054
Hemoglobin A1b is a minor hemoglobin component from human hemolysate (less than 0.5% of total hemoglobin) whose structure has never been established. It was purified and studied by mass spectrometry. Electrospray ionization of its abnormal beta-chain indicated a 70-Da mass increase. Separation of the trytic digest by reversed-phase liquid chromatography revealed an abnormal beta T1 peptide. Cesium ion bombardment ionization produced a protonated molecular ion at m/z 1022.516, showing an additional C3H2O2 residue to normal beta T1. The amino acid sequences of both abnormal and normal beta T1 peptides were found identical by comparison of their collision activation spectra. Time course hydrolysis of abnormal beta T1 indicated a rapid loss of the modifying group, leading to normal beta T1. At least, mild treatment with acidic methanol showed an additional methylated site, comparatively with normal beta T1. All these results are consistent with a ketimine-linked pyruvic acid at the amino end of the beta-chain of hemoglobin. 相似文献
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Mario Stampanoni Bassi Tommaso Nuzzo Luana Gilio Mattia Miroballo Alessia Casamassa Fabio Buttari Paolo Bellantonio Roberta Fantozzi Giovanni Galifi Roberto Furlan Annamaria Finardi Arianna De Rosa Anna Di Maio Francesco Errico Diego Centonze Alessandro Usiello 《Journal of neurochemistry》2021,159(5):857-866
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Timmers LF Ducati RG Sánchez-Quitian ZA Basso LA Santos DS de Azevedo WF 《Journal of molecular modeling》2012,18(2):467-479
Cytidine Deaminase (CD) is an evolutionarily conserved enzyme that participates in the pyrimidine salvage pathway recycling cytidine and deoxycytidine
into uridine and deoxyuridine, respectively. Here, our goal is to apply computational techniques in the pursuit of potential
inhibitors of Mycobacterium tuberculosis CD (MtCDA) enzyme activity. Molecular docking simulation was applied to find the possible hit compounds. Molecular dynamics simulations
were also carried out to investigate the physically relevant motions involved in the protein-ligand recognition process, aiming
at providing estimates for free energy of binding. The proposed approach was capable of identifying a potential inhibitor,
which was experimentally confirmed by IC50 evaluation. Our findings open up the possibility to extend this protocol to different databases in order to find new potential
inhibitors for promising targets based on a rational drug design process. 相似文献