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21.
Sarit Sara Sivan Ellen Wachtel Peter Roughley 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Aggrecan is the major non-collagenous component of the intervertebral disc. It is a large proteoglycan possessing numerous glycosaminoglycan chains and the ability to form aggregates in association with hyaluronan. Its abundance and unique molecular features provide the disc with its osmotic properties and ability to withstand compressive loads. Degradation and loss of aggrecan result in impairment of disc function and the onset of degeneration.Scope of review
This review summarizes current knowledge concerning the structure and function of aggrecan in the normal intervertebral disc and how and why these change in aging and degenerative disc disease. It also outlines how supplementation with aggrecan or a biomimetic may be of therapeutic value in treating the degenerate disc.Major conclusions
Aggrecan abundance reaches a plateau in the early twenties, declining thereafter due to proteolysis, mainly by matrix metalloproteinases and aggrecanases, though degradation of hyaluronan and non-enzymic glycation may also participate. Aggrecan loss is an early event in disc degeneration, although it is a lengthy process as degradation products may accumulate in the disc for decades. The low turnover rate of the remaining aggrecan is an additional contributing factor, preventing protein renewal. It may be possible to retard the degenerative process by restoring the aggrecan content of the disc, or by supplementing with a bioimimetic possessing similar osmotic properties.General significance
This review provides a basis for scientists and clinicians to understand and appreciate the central role of aggrecan in the function, degeneration and repair of the intervertebral disc. 相似文献22.
Franziska Stehle Kristin SchulzBarbara Seliger 《Biochimica et Biophysica Acta - Proteins and Proteomics》2014,1844(5):909-916
An impressive, but often short objective response was obtained in many tumor patients treated with different targeted therapies, but most of the patients develop resistances against these drugs. So far, a number of distinct mechanisms leading to intrinsic as well as acquired resistances have been identified in tumors of distinct origin. These can arise from genetic alterations, like mutations, truncations, and amplifications or due to deregulated expression of various proteins and signal transduction pathways, but also from cellular heterogeneity within tumors after an initial response. Therefore, biomarkers are urgently needed for cancer prognosis and personalized cancer medicine. The application of “ome”-based technologies including cancer (epi)genomics, next generation sequencing, cDNA microarrays and proteomics might led to the predictive or prognostic stratification of patients to categorize resistance mechanisms and to postulate combinations of treatment strategies. This review discusses the implementation of proteome-based analysis to identify markers of pathway (in)activation in tumors and the resistance mechanisms, which represent major clinical problems as a tool to optimize individually tailored therapies based on targeted drugs. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. 相似文献
23.
钙离子是一个多功能的第二信使,在植物响应各种生理刺激时,Ca2+参与调节植物的多种生长发育和胁迫适应过程。在这些过程中,Ca2+信号带有特异性标签,通过Ca2+结合蛋白及其下游靶蛋白感知不同刺激并翻译成响应的细胞反应。钙调素(CaM)和钙调素类蛋白(CML)是Ca2+主要感受器,通过调节不同靶蛋白的活性调控多种细胞功能。最近在植物对抗病原菌的防卫反应中有关Ca2+/CaM信号转导系统的研究取得了一定进展。重点关注植物免疫应答过程中受CaM/CML调控的信号组分的研究,包括参与Ca2+信号产生和Ca2+依赖的表达基因组分调控。 相似文献
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Alessandra Becker Finco Ricardo Andrez Machado-de-Ávila Rayana Maciel Juliana De Moura Philippe Billiald Andrea Emilia Marques Stinghen Larissa M. Alvarenga 《Biochemistry and Biophysics Reports》2016
Advanced Glycation End Products (AGEs) are toxins that are involved in structural and functional alterations of several organs and tissues, resulting in various pathologies. Several types of AGEs have been described but carboxymethyllysine (CML) is the major antigenic AGE compound. In this study, three different immunogenic carrier proteins (KLH, keyhole limpet hemocyanin; BSA, bovine serum albumin; and HSA, human serum albumin) were modified by glycation. The glycated molecules were used to produce epitope-specific monoclonal antibodies able to recognize the CML domain and to detect uremic toxins in the serum of patients with chronic kidney disease (CKD). A competitive ELISA was standardized in order to quantify CML in the sera of CKD patients. An increase in uremic toxins can compromise the clinical condition of these patients, thus, the detection and quantification of these toxins should contribute to a better management and understanding of this disease. 相似文献
26.
A Orlacchio C Maffei C Emiliani P Rambotti S Davis 《Biochemical and biophysical research communications》1984,122(3):966-973
The beta-hexosaminidase (EC 3.2.1.30) isoenzymes were separated on the basis of their carbohydrate moieties by an affinity chromatography using immobilized phenylboronate. Normal lymphocytes and granulocytes contain two major forms of beta-hexosaminidase, acute lymphoblastic, acute myeloblastic, chronic lymphocytic and chronic myelocytic leukemic cells contain an extra, distinct isoenzyme of beta-hexosaminidase. This extra isoenzyme may be a marker for the leukemic conversion of hematopoietic tissue. 相似文献
27.
IFN-α regulates IL 10 production by CML cells in vitro 总被引:1,自引:0,他引:1
Graham Pawelec Elke Schlotz Arnika Rehbein 《Cancer immunology, immunotherapy : CII》1999,48(8):430-434
High levels of spontaneous in vitro IL 10 secretion by a subset of untreated chronic phase CML patients' cells are shown
to be decreased in the presence of IFN-α. However, the lower level of spontaneous IL 10 secretion by healthy control cells
are was not depressed by IFN-α. In contrast to its effects on IL 10 production, IFN-α increased the low spontaneous secretion
of IL 1α by patients' cells, bud did not further increase the higher levels of spontaneous IL 1β secretion by normal cells.
It had no effect on secretion of TNF-α by patients or normals. Spontaneous secretion of IL-1α (or IFN-γ) by patients' cells
was not observed whether or not IFN-α was present. Therefore, one mechanism of action of IFN-α in vivo may involve decreasing
endogenous IL 10 secretion (thereby reducing suppressive effects on T cell reactivity) and increasing IL 1β secretion (thereby
enhancing antigen presentation).
Received: November 1998 / Accepted: 1 March 1999 相似文献
28.
Kyle W. Bender Daniel M. Rosenbaum Barbara Vanderbeld Midhat Ubaid Wayne A. Snedden 《The Plant journal : for cell and molecular biology》2013,76(4):634-647
During Ca2+ signal transduction, Ca2+‐binding proteins known as Ca2+ sensors function to decode stimulus‐specific Ca2+ signals into downstream responses. Plants possess extended families of unique Ca2+ sensors termed calmodulin‐like proteins (CMLs) whose cellular roles are not well understood. CML39 encodes a predicted Ca2+ sensor whose expression is strongly increased in response to diverse external stimuli. In the present study, we explored the biochemical properties of recombinant CML39, and used a reverse genetics approach to investigate its physiological role. Our data indicate that Ca2+ binding by CML39 induces a conformational change in the protein that results in an increase in exposed‐surface hydrophobicity, a property that is consistent with its predicted function as a Ca2+ sensor. Loss‐of‐function cml39 mutants resemble wild‐type plants under normal growth conditions but exhibit persistent arrest at the seedling stage if grown in the absence of sucrose or other metabolizable carbon sources. Under short‐day conditions, cml39 mutants display increased sucrose‐induced hypocotyl elongation. When grown in the dark, cml39 mutants show impaired hypocotyl elongation in the absence of sucrose. Promoter–reporter data indicate that CML39 expression is prominent in the apical hook in dark‐grown seedlings. Collectively, our data suggest that CML39 functions in Arabidopsis as a Ca2+ sensor that plays an important role in the transduction of light signals that promote seedling establishment. 相似文献
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Sphingolipids function as bioactive mediators of different cellular processes, mostly proliferation, survival, differentiation and apoptosis, besides being structural components of cellular membranes. Involvement of sphingolipid metabolism in cancerogenesis was demonstrated in solid tumors as well as in hematological malignancies. Herein, we describe the main biological and clinical aspects of leukemias and summarize data regarding sphingolipids as mediators of apoptosis triggered in response to anti-leukemic agents and synthetic analogs as inducers of cell death as well. We also report the contribution of molecules that modulate sphingolipid metabolism to development of encouraging strategies for leukemia treatment. Finally we address how deregulation of sphingolipid metabolism is associated to occurrence of therapy resistance both in vitro and in vivo. Sphingolipids can be considered promising therapeutic tools alone or in combination with other compounds, as well as valid targets in the attempt to eradicate leukemia and overcome drug resistance. 相似文献