ISSN:0892-6638    

DOI:10.1096/fasebj.7.13.8405804

出版商:Wiley    

年代:1993

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.7.13.8405805

出版商:Wiley    

年代:1993

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/j.1530-6860.1993.tb93355.x

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

The elastic properties of many tissues such as the lung, dermis, and large blood vessels are due to the presence of elastic fibers in the extracellular space. These fibers have been shown by biochemical and ultrastructural analysis to be composed of two distinct components, a more abundant amorphous component and a 10–12 nm microfibrillar component, which is located primarily around the periphery of the amorphous component. The protein elastin makes up the highly insoluble amorphous component and is responsible for the elastic properties, Elastin is found throughout the vertebrate kingdom and possesses an unusual chemical composition rich in glycine, proline, and hydrophobic amino acids, consonant with its characteristic physical properties. The 72‐kDa biosynthetic precursor, tropoelastin, is secreted into the extracellular space where it becomes highly cross‐linked into a rubber‐like network through the activity of the copper‐requiring enzyme lysyl oxidase. Analysis of the elastin gene has demonstrated that hydrophobic and cross‐linking domains are encoded in separate exons and that there is significant alternative splicing, resulting in multiple isoforms of tropoelastin. The elastin gene promoter contains many potential binding sites for various modulating factors indicative of a complex pattern of transcriptional regulation. The microfibrils contain several proteins, including fibrillin, and probably act as an organizing scaffold in the formation of the elastin network. There appears to be a fibrillin gene family in which each protein contains multiple repeats of a motif previously found in epidermal growth factor and a second motif observed in transforming growth factorβ1‐binding protein. Mutations in the fibrillin gene located on human chromosome 15 have been strongly implicated as the cause of the Marfan syndrome.—Rosenbloom, J., Abrams, W. R., Mecham, R. The elastic fiber.FASEB J.7: 1208‐1218; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.13.8405806

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Historically, great minds have been tantalized by the idea that integers contain hidden, subtle meanings that could give us deep insights into natural (and supernatural) phenomena. Numerological analysis has been used in religion, mythology, and the sciences. In the field of proteins, integers played a stimulating role during early struggles to unravel structure, but they ultimately proved constrictive and misleading. In contrast, the introduction of imaginary (or complex) numbers into the algebra and numerical analysis of ligand‐protein affinities can open new perspectives into such interactions.—Klotz, I. M. Number mysticism in protein thinking.FASEB J.7: 1219‐1225; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.13.8405807

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

The central nervous system (CNS) can be invaded and damaged by a variety of microbes. The host response to such injury involves CNS cells, and in many cases hematogenous cells also. Recent experiments indicate that astrocytes, macroglial resident cells of the CNS, play key roles in this process. The astroglial production of trophic factors and elimination of neurotoxins are likely to fulfill important protective and reparative functions during CNS infection. In addition, astrocytes could, in concert with microglial cells, regulate the recruitment and activity of infiltrating hematogenous cells through their expression of cytokines, proteases, protease inhibitors, adhesion molecules, and extracellular matrix components. Although previous experiments suggested that astrocytes might initiate inflammatory demyelinating disease by presenting CNS antigens to autoreactive immune cells, current evidence points against such a detrimental activity. In view of the generally beneficial role of astrocytes, impairments of astroglial function by microbes or host‐derived factors have the potential to contribute to neurologic disease. Diseases in which this pathogenetic process may be relevant include HIV‐1‐associated cognitive/motor complex and spongiform encephalopathies.—Mucke, L., Eddleston, M. Astrocytes in infectious and immune‐mediated diseases of the central nervous system.FASEB J.7: 1226‐1232; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.13.8405808

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

The high molecular weight glycosaminoglycan hyaluronan plays an important role in tissue remodeling during development, normal tissue homeostasis, and disease. The interaction of hyaluronan with matrix hyaluronan‐binding proteins and cell‐surface hyaluronan receptors regulates many aspects of cell behavior such as cell migration, cell‐cell adhesion, and cell differentiation. Hyaluronan‐binding proteins have been grouped together as a family termed hyaladherins — further subdivided in matrix and cell‐surface hyaladherins (receptors). Specific hyaluronan‐hyaladherin interactions that affect cell behavior are the focus of this review. Both clearance and turnover of hyaluronan involve hyaluronan receptor‐mediated endocytosis. Pericellular matrix assembly and retention on many cells, especially chondrocytes, are mediated by hyaluronan receptors, in coordination with other matrix hyaladherins. Hyaluronan can also have an independent, direct effect on cell‐to‐cell adhesion as well as migration, again mediated by specific cell‐surface hyaluronan receptors. This is especially apparent in tumor cells, where metastatic potential is correlated with hyaluronan receptor expression. As migrating cells encounter new environments enriched in matrix hyaladherins, the capacity for matrix assembly may terminate cell migration. Thus, the temporal/spatial deposition of particular matrix hyaladherins also serves as signals or matrix cues to alter cell behavior.—Knudson, C. B., Knudson, W. Hyaluronan‐binding proteins in development, tissue homeostasis, and disease.FASEB J.7: 1233‐1241; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.13.7691670

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Organ damage can occur quickly when blood flow is compromised. Lactic acidosis has long been associated with such ischemia, and many physicians assume that organ damage is caused by this acidosis. However, reviewing the literature related to hypoxia and ischemia reveals little data to support the concept of acidosis as damaging to tissue. In contrast, recent studies indicate that the acidosis is actually protective, even during reperfusion when cellular damage may occur. Reperfusion is accompanied by generation of free radicals and other reactive species that can damage proteins, membranes, and nucleic acids, supporting an emerging view that implicates these reactive species in the actual tissue damage. The critical targets of the damaging species are not known, but reaction with key enzymes and structural proteins could certainly disrupt organ function. Cellular proteins are oxidatively modified during reperfusion, in part by metal‐catalyzed oxidation in which cellular iron plays a key role. Metal‐catalyzed oxidation of proteins may be important in the pathogenesis of other disorders, including the potentially blinding disease, retinopathy of the premature.—Levine, R. L. Ischemia: From acidosis to oxidation.FASEB J.7: 1242‐1246; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.13.8405809

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Aspartylglycosaminuria (AGU) (McKusick 20840) is the most common disorder of glycoprotein degradation caused by the failure of lysosomes to digest the protein‐to‐carbohydrate linkage of Asn‐linked glycoproteins. During the past few years there has been significant progress in our understanding of both the protein chemistry and molecular biology of glycosylasparaginase (EC 3.5.1.26) as well as the molecular changes underlying the storage disease AGU that results from deficiency of this lysosomal hydrolase. Modern clinical assays have been developed for the diagnosis and carrier detection of this disease. Detailed structure, substrate specificity, mechanism of action, and a part of the active site of glycosylasparaginase have been defined. Molecular biology of glycosylasparaginase has progressed rapidly and already some mutations in the glycosylasparaginase gene resulting in AGU have been identified. Evolutionary aspects based on sequence data indicate a mechanistic relationship between mammalian glycosylasparaginases and bacterial/plant asparaginases.—Mononen, I., Fisher, K. J., Kaartinen, V., Aronson, N. N., Jr. Aspartylglycosaminuria: protein chemistry and molecular biology of the most common lysosomal storage disorder of glycoprotein degradation.FASEB J.7: 1247‐1256; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.13.8405810

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Trypanosoma cruzi, the agent of Chagas' disease, an ailment characterized by a progressive chronic fibrotic myocarditis and degeneration of tissues that are innervated by the autonomic nervous system, is a voracious sialic acid eater from glycoconjugates of the surrounding medium. This is accomplished through an active trans‐sialidase residing on the surface membrane of the trypomastigote stage, which is the parasite form that invades vertebrate cells. The existence of the enzyme was proposed and established only 7 years ago and yet a flood of information on the subject is already available.Trans‐sialidase is able to reversibly transfer sialic acidα(2å3)‐linked to an external Galβfrom the host cell surface sialoglycoconjugates to a terminal Galβof an appropriate acceptor on the parasite surface. In the absence of an acceptor, the enzyme acts as a hydrolase transferring sialic acid to water.Trans‐sialidase belongs to a highly heterogeneous gene family of surface molecules sharing with each other and with bacterial neuraminidases variable degrees of nucleotide sequence homology and common motifs. It has been proposed that sialylation of the parasite surface catalyzed bytrans‐sialidase is necessary for successful invasion of the host cell, but the evidence available is still indirect. Another function could be a protection from lysis by the alternative pathway of complement while the parasite is circulating in the acute phase of the disease.—Colli, W.Trans‐sialidase: a unique enzyme activity discovered in the protozoanTrypanosoma cruzi.FASEB J.7: 1257‐1264; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.13.8405811

出版商:Wiley    

年代:1993

数据来源: WILEY