共查询到20条相似文献，搜索用时 15 毫秒
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F.M. Lampert C. Kütscher G.B. Stark G. Finkenzeller 《Journal of cellular biochemistry》2016,117(3):760-768
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Xizhong Sui Hongchao Wei Dacheng Wang 《Journal of cellular and molecular medicine》2015,19(8):1773-1782
Transforming growth factor (TGF)‐β1 is a known factor in angiotensin II (Ang II)‐mediated cardiac fibrosis after myocardial infarction (MI). Hypoxia inducible factor‐1 (Hif‐1α) was recently demonstrated to involve in the tissue fibrosis and influenced by Ang II. However, whether Hif‐1α contributed to the Ang II‐mediated cardiac fibrosis after MI, and whether interaction or synergetic roles between Hif‐1α and TGF‐β pathways existed in the process was unclear. In vitro, cardiac cells were incubated under hypoxia or Ang II to mimic ischaemia. In vivo, valsartan was intravenously injected into Sprague–Dawley rats with MI daily for 1 week; saline and hydralazine (another anti‐hypertensive agent like valsartan) was used as control. The fibrosis‐related proteins were detected by Western blotting. Cardiac structure and function were assessed with multimodality methods. We demonstrated in vitro that hypoxia would induce the up‐regulation of Ang II, TGF‐β/Smad and Hif‐1α, which further induced collagen accumulation. By blocking with valsartan, a blocker of Ang II type I (AT1) receptor, we confirmed that the up‐regulation of TGF‐β/Smad and Hif‐1α was through the Ang II‐mediated pathway. By administering TGF‐β or dimethyloxalylglycine, we determined that both TGF‐β/Smad and Hif‐1α contributed to Ang II‐mediated collagen accumulation and a synergetic effect between them was observed. Consistent with in vitro results, valsartan significantly attenuated the expression of TGF‐β/Smad, Hif‐1α and fibrosis‐related protein in rats after MI. Heart function, infarcted size, wall thickness as well as myocardial vascularization of ischaemic hearts were also significantly improved by valsartan compared with saline and hydralazine. Our study may provide novel insights into the mechanisms of Ang II‐induced cardiac fibrosis as well as into the cardiac protection of valsartan. 相似文献
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Xiaojian Huang Bowei Ni Zekai Mao Yang Xi Xiangyu Chu Rui Zhang Xiaohu Ma Hongbo You 《Journal of cellular and molecular medicine》2019,23(11):7525-7534
Osteoarthritis (OA), an age‐related degenerative joint disease, is pathologically characterized by articular cartilage degeneration and synovial inflammation. Nephroblastoma overexpressed (NOV or CCN3), a matricellular protein, is a primary member of the CCN family (Cyr61, Ctgf, NOV) of proteins and is involved in various inflammatory disorders. Previous studies reported that CCN3 might play a therapeutic role in OA. However, the underlying mechanism remains unclear. In this study, we confirmed the expression of CCN3 was decreased in human and rat OA articular cartilage. Recombinant CCN3 ameliorated the IL‐1β‐induced matrix catabolism, as demonstrated by MMP1, MMP3, MMP13, ADAMTS5 and iNOS expression, in vitro. In addition, the degradation of cartilage matrix such as collagen 2 and aggrecan could be reversed by CCN3. Furthermore, we found CCN3 promoted autophagy as Atg5, Beclin1 and LC3‐II expression were increased. High‐mobility group box 1 was negatively correlated with CCN3 in IL‐1β‐induced osteoarthritis responses, and HMGB1 is involved in the protective effect of CCN3 in OA. Moreover, CCN3 overexpression decreased the expression of HMGB1 and reversed the IL‐1β induced MMPs production. Additionally, recombinant CCN3 or CCN3 overexpression attenuated the activation of PI3K/AKT/mTOR pathway induced by IL‐1β. Our study presents new mechanisms of CCN3 in osteoarthritis and indicates that CCN3 can serve as a novel potential therapeutic target for osteoarthritis. 相似文献
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Markus G. Rudolph Matthew S. Kelker Thomas R. Schneider Todd O. Yeates Vanessa Oseroff David K. Heidary Patricia A. Jennings Ian A. Wilson 《Acta Crystallographica. Section D, Structural Biology》2003,59(2):290-298
The crystal structure at 1.54 Å resolution of a double mutant of interleukin‐1β (F42W/W120F), a cytokine secreted by macrophages, was determined by multiple‐wavelength anomalous dispersion (MAD) using data from highly twinned selenomethionine‐modified crystals. The space group is P43, with unit‐cell parameters a = b = 53.9, c = 77.4 Å. Self‐rotation function analysis and various intensity statistics revealed the presence of merohedral twinning in crystals of both the native (twinning fraction α≃ 0.35) and SeMet (α≃ 0.40) forms. Structure determination and refinement are discussed with emphasis on the possible reasons for successful phasing using untreated twinned MAD data. 相似文献
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《Peptide Science》2017,108(3)
The conformational characteristics of protected homo‐oligomeric Boc‐[β3(R)Val]n‐OMe, n = 1, 2, 3, 4, 6, 9, and 12 have been investigated in organic solvents using nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) absorption spectroscopy and circular dichroism (CD) methods. The detailed 1H NMR analysis of Boc‐[β3(R)Val]12‐OMe reveals that the peptide aggregates extensively in CDCl3, but is disaggregated in 20%, (v/v) dimethyl sulfoxide (DMSO) in CDCl3 and in CD3OH. Limited assignment of the N‐terminus NH groups, together with solvent dependence of NH chemical shifts and temperature coefficients provides evidence for 14‐helix conformation in the 12‐residue peptide. FTIR analysis in CHCl3 establishes that the onset of folding and aggregation, as evidenced by NH stretching bands at 3375 cm−1 (intramolecular) and 3285 cm−1 (intermolecular), begins at the level of the tetrapeptide. The observed CD bands, 214 nm (negative) and 198 nm (positive), support 14‐helix formation in the 9 and 12 residue sequences. The folding and aggregation tendencies of homo‐oligomeric α‐, β‐, and γ‐ residues is compared in the model peptides Boc‐[ωVal]n‐NHMe, ω = α, β, and γ and n = 1, 2, and 3. Analysis of the FTIR spectra in CHCl3, establish that the tendency to aggregate at the di and tripeptide level follows the order β > α∼γ, while the tendency to fold follows the order γ > β > α. 相似文献
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Nobuo Okazaki Maki Kumei Miho Manzoku Seiki Kuramitsu Mikako Shirouzu Akeo Shinkai Shigeyuki Yokoyama 《Acta Crystallographica. Section F, Structural Biology Communications》2007,63(3):173-177
TTHA0281 is a hypothetical protein from Thermus thermophilus HB8 that belongs to an uncharacterized protein family, UPF0150, in the Pfam database and to COG1598 in the National Center for Biotechnology Information Database of Clusters of Orthologous Groups. The X‐ray crystal structure of the protein was determined by a multiple‐wavelength anomalous dispersion technique and was refined at 1.9 Å resolution to a final R factor of 18.5%. The TTHA0281 monomer adopts an α‐β‐β‐β‐α fold and forms a homotetramer. Based on the properties and functions of structural homologues of the TTHA0281 monomer, the TTHA0281 protein is speculated to be involved in RNA metabolism, including RNA binding and cleavage. 相似文献
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Ann L Cornish Caroline E Sutton Joanne O'Donnell Louise H Cengia Andrew W Roberts Ian P Wicks Kingston H G Mills Ben A Croker 《EMBO reports》2010,11(8):640-646
Reports describing the effect of interferon‐γ (IFNγ) on interleukin‐1β (IL‐1β) production are conflicting. We resolve this controversy by showing that IFNγ potentiates IL‐1β release from human cells, but transiently inhibits the production of IL‐1β from mouse cells. Release from this inhibition is dependent on suppressor of cytokine signalling 1. IL‐1β and Th17 cells are pathogenic in mouse models for autoimmune disease, which use Mycobacterium tuberculosis (MTB), in which IFNγ and IFNβ are anti‐inflammatory. We observed that these cytokines suppress IL‐1β production in response to MTB, resulting in a reduced number of IL‐17‐producing cells. In human cells, IFNγ increased IL‐1β production, and this might explain why IFNγ is detrimental for multiple sclerosis. In mice, IFNγ decreased IL‐1β and subsequently IL‐17, indicating that the adaptive immune response can provide a systemic, but transient, signal to limit inflammation. 相似文献
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Wooi Koon Wang Mark Bycroft Nicholas W. Foster Ashley M. Buckle Alan R. Fersht Yu Wai Chen 《Acta Crystallographica. Section D, Structural Biology》2001,57(4):545-551
p73 is a homologue of the tumour suppressor p53 and contains all three functional domains of p53. The α‐splice variant of p73 (p73α) contains near its C‐terminus an additional structural domain known as the sterile α‐motif (SAM) that is probably responsible for regulating p53‐like functions of p73. Here, the 2.54 Å resolution crystal structure of this protein domain is reported. The crystal structure and the published solution structure have the same five‐helix bundle fold that is characteristic of all SAM‐domain structures, with an overall r.m.s.d. of 1.5 Å for main‐chain atoms. The hydrophobic core residues are well conserved, yet some large local differences are observed. The crystal structure reveals a dimeric organization, with the interface residues forming a mini four‐helix bundle. However, analysis of solvation free energies and the surface area buried upon dimer formation indicated that this arrangement is more likely to be an effect of crystal packing rather than reflecting a physiological state. This is consistent with the solution structure being a monomer. The p73α SAM domain also contains several interesting structural features: a Cys‐X‐X‐Cys motif, a 310‐helix and a loop that have elevated B factors, and short tight inter‐helical loops including two β‐turns; these elements are probably important in the normal function of this domain. 相似文献
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Pu Wang Pei‐Pei Guan Jing‐Wen Guo Long‐Long Cao Guo‐Biao Xu Xin Yu Yue Wang Zhan‐You Wang 《Aging cell》2016,15(5):861-871
Cyclooxygenase‐2 (COX‐2) has been recently identified to be involved in the pathogenesis of Alzheimer's disease (AD). Yet, the role of an important COX‐2 metabolic product, prostaglandin (PG) I2, in the pathogenesis of AD remains unknown. Using human‐ and mouse‐derived neuronal cells as well as amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice as model systems, we elucidated the mechanism of anterior pharynx‐defective (APH)‐1α and pharynx‐defective‐1β induction. In particular, we found that PGI2 production increased during the course of AD development. Then, PGI2 accumulation in neuronal cells activates PKA/CREB and JNK/c‐Jun signaling pathways by phosphorylation, which results in APH‐1α/1β expression. As PGI2 is an important metabolic by‐product of COX‐2, its suppression by NS398 treatment decreases the expression of APH‐1α/1β in neuronal cells and APP/PS1 mice. More importantly, β‐amyloid protein (Aβ) oligomers in the cerebrospinal fluid (CSF) of APP/PS1 mice are critical for stimulating the expression of APH‐1α/1β, which was blocked by NS398 incubation. Finally, the induction of APH‐1α/1β was confirmed in the brains of patients with AD. Thus, these findings not only provide novel insights into the mechanism of PGI2‐induced AD progression but also are instrumental for improving clinical therapies to combat AD. 相似文献
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Hideki Hirose Atsushi Sasaki Nana Ishii Masaru Sekijima Takahiro Iyama Toshio Nojima Yoshikazu Ugawa 《Bioelectromagnetics》2010,31(2):104-112
Given the widespread use of the cellular phone today, investigation of potential biological effects of radiofrequency (RF) fields has become increasingly important. In particular, much research has been conducted on RF effects on brain function. To examine any biological effects on the central nervous system (CNS) induced by 1950 MHz modulation signals, which are controlled by the International Mobile Telecommunication‐2000 (IMT‐2000) cellular system, we investigated the effect of RF fields on microglial cells in the brain. We assessed functional changes in microglial cells by examining changes in immune reaction‐related molecule expression and cytokine production after exposure to a 1950 MHz Wideband Code Division Multiple Access (W‐CDMA) RF field, at specific absorption rates (SARs) of 0.2, 0.8, and 2.0 W/kg. Primary microglial cell cultures prepared from neonatal rats were subjected to an RF or sham field for 2 h. Assay samples obtained 24 and 72 h after exposure were processed in a blind manner. Results showed that the percentage of cells positive for major histocompatibility complex (MHC) class II, which is the most common marker for activated microglial cells, was similar between cells exposed to W‐CDMA radiation and sham‐exposed controls. No statistically significant differences were observed between any of the RF field exposure groups and the sham‐exposed controls in percentage of MHC class II positive cells. Further, no remarkable differences in the production of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6) were observed between the test groups exposed to W‐CDMA signal and the sham‐exposed negative controls. These findings suggest that exposure to RF fields up to 2 W/kg does not activate microglial cells in vitro. Bioelectromagnetics 31:104–112, 2010. © 2009 Wiley‐Liss, Inc. 相似文献
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Jinyoung Son Misun Kim Ilo Jou Kyoung Chan Park Hee Young Kang 《Pigment cell & melanoma research》2014,27(2):201-208
Inflammatory cytokines are closely related to pigmentary changes. In this study, the effects of IFN‐γ on melanogenesis were investigated. IFN‐γ inhibits basal and α‐MSH‐induced melanogenesis in B16 melanoma cells and normal human melanocytes. MITF mRNA and protein expressions were significantly inhibited in response to IFN‐γ. IFN‐γ inhibited CREB binding to the MITF promoter but did not affect CREB phosphorylation. Instead, IFN‐γ inhibited the association of CBP and CREB through the increased association between CREB binding protein (CBP) and STAT1. These findings suggest that IFN‐γ inhibits both basal and α‐MSH‐induced melanogenesis by inhibiting MITF expression. The inhibitory action of IFN‐γ in α‐MSH‐induced melanogenesis is likely to be associated with the sequestration of CBP via the association between CBP and STAT1. These data suggest that IFN‐γ plays a role in controlling inflammation‐ or UV‐induced pigmentary changes. 相似文献
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Hyunju Kim Yu‐Ran Na So Yeon Kim Eun Gyeong Yang 《Journal of cellular biochemistry》2016,117(3):647-658
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Xin Li Jina Lim Jinxiu Lu Taylor M Pedego Linda Demer Yin Tintut 《Journal of cellular biochemistry》2015,116(10):2354-2364
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