ISSN:0892-6638    

DOI:10.1096/fasebj.7.5.8462779

出版商:Wiley    

年代:1993

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.7.5.8462780

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Residualizing labels (R‐labels) are chemical tags for proteins, originally designed for studies of the sites and mechanisms of plasma protein catabolism. The labels consist of oligosaccharides derivatized with radioactive, fluorescent, nuclear magnetic resonance (NMR), or positron emission tomography (PET) active reporter molecules. Because these glycoconjugates generally have molecular masses in excess of 500 daltons and are hydrophilic, they are relatively membrane impermeant. They are also designed to be resistant to lysosomal hydrolases and are therefore retained inside cells with half‐lives of 2–5 days after endocytosis and degradation of the carrier protein. The R‐labels thus provide a convenient means for following the cumulative uptake and catabolism of proteins by cells in vivo or in vitro. This review summarizes how R‐labels have provided insights into the sites and regulation of the turnover of circulating proteins, and pathways for intracellular transport and degradation of endocytosed proteins. The potential use of R‐labels for noninvasive studies of the distribution of protein pharmaceuticals in vivo is also discussed.— Thorpe, S. R., Baynes, J. W., and Chroneos, Z. C. The design and application of residualizing labels for studies of protein catabolism.FASEB J.7: 3 99‐405; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.5.8462781

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Nearly all human oral bacteria exhibit coaggregation, cell‐to‐cell recognition of genetically distinct cell types. Clumps or coaggregates composed of the two kinds of cells are formed immediately upon mixing two partner cell types. Members of all 18 genera tested exhibit lactose‐reversible coaggregation. Many of these interactions appear to be mediated by a lectin on one cell type that interacts with a complementary carbohydrate receptor on the other cell type. A lactose‐sensitive adhesin has been isolated fromPrevotella loescheiiPK1295, and it exhibits the adherence properties observed with whole cells. Other adhesins have been identified and the genes for some of them have been cloned and sequenced. OneStreptococcus sanguisadhesin is a lipoprotein that appears to have a dual function of recognizing both a bacterial carbohydrate receptor and a receptor in human saliva. Carbohydrate receptors for some adhesins have been purified from five oral streptococci, and they specifically block the coaggregations with the streptococcal partners that express the complementary adhesins. Coaggregation offers an explanation for the temporally related accretion of dental plaque and bacterial recognition of mucosal surfaces. Early colonizers of the tooth surface coaggregate with each other and late colonizers of the tooth surface coaggregate with each other, but with few exceptions, early colonizers do not recognize late colonizers. Furthermore, bacteria that colonize mucosal surfaces coaggregate with each other, indicating the high degree of specificity of coaggregation in the oral bacterial population.— Kolenbrander, P. E., Ganeshkumar, N., Cassels, F. J., Hughes, C. V. Coaggregation: specific adherence among human oral plaque bacteria.FASEB J.7: 406‐413; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.5.8462782

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

The steroid hormone intermediate, DHEA, has been proposed as a therapeutic agent for the treatment of obesity. Its effects on lipogenesis, substrate cycling, peroxisome proliferation, mitochondrial respiration, protein synthesis, and thyroid hormone function have been reported. The results of these studies suggest that the antiobesity function of DHEA is not simply one of inhibiting fat synthesis and deposition but is one of affecting a number of pathways that contribute to the maintenance of the isoenergetic state rather than the promotion of positive energy balance.— Berdanier, C. D., Parente, J. A., Jr., McIntosh, M. K. Is dehydroepiandrosterone an antiobesity agent?FASEB J.7: 414‐419; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.5.8462783

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

CD45, a family of hematopoietic cell specific surface antigens, is the best characterized protein tyrosine phosphatase described to date. Considerable evidence from a number of laboratories suggests that surface expression of this molecule is required for normal signaling events to occur in T lymphocytes, B lymphocytes, and natural killer cells. In this paper, data supporting this contention are reviewed and a model proposing how CD45 may exert its regulatory function on signal transduction via the T cell antigen receptor is presented.— Koretzky, G. A. Role of the CD45 tyrosine phosphatase in signal transduction in the immune system.FASEB J.7: 420‐426; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.5.8462784

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Regulation of gene expression in response to steroids, thyroid hormone, and retinoids is mediated by an impressive array of intracellular receptors. Sequence analysis showed that the hormone receptors comprise a large superfamily of ligand‐responsive transcription factors. Upon binding to hormones, the receptors interact with specific hormone response elements located in the promoters of numerous genes. Promoter‐bound receptors communicate with distinct receptors and/or additional members of the transcriptional machinery, frequently evoking protein‐protein interactions. Ultimately, this results in the induction of complex gene systems that control hormone‐induced processes such as differentiation, cell growth, and homeostasis. In addition to the genes transcribed by RNA polymerase II, the lipophilic hormones, particularly glucocorticoids, can also modulate RNA polymerase I‐directed transcription of the ribosomal gene. For both transcription systems, activation and repression of genes in response to hormones have been reported. Finally, the involvement of hormone receptors in tumorigenesis has been discussed. It is likely that receptor studies will have major implications in the diagnosis and therapy of diseases such as leukemia.— Reichel, R. R., Jacob, S. T. Control of gene expression by lipophilic hormones.FASEB J.7: 42 7‐436; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.5.8385039

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Idiotopes are markers on the variable domains of antigen‐specific immunological receptors recognized by anti‐idiotypic antibodies or T cells. Therefore, a given antibody or T cell receptor can be identified on the basis of a characteristic idiotypic pattern. The structural correlates for idiotopes on antibodies have been studied by competitive binding assays, electron microscopy, site‐directed mutagenesis, and X‐ray crystallography. Immunoglobulin idiotopes, recognized by anti‐idiotypic antibodies, can involve amino acid residues from several hypervariable or framework regions and from either or both of the heavy and light chain variable domains. Recent studies suggest that it may be possible to exploit structural knowledge of idiotopes and anti‐idiotopes for the design of new ligands for immunological or other cell surface receptors. In one instance, it has been possible to use the inferred structural features of an anti‐idiotope, which mimics a viral protein, to design a small organic molecule with functional properties approximating those of the antigen and the native anti‐idiotope. An alternative strategy being explored for creating new vaccines or therapeutic agents involves engineering an amino acid sequence, corresponding to a segment of a selected nominal antigen, into an immunoglobulin variable domain.— Greenspan, N. S., Bona, C. A. Idiotypes: structure and immunogenicity.FASEB J.7: 437‐444; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.5.8462785

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

The unique and characteristic feature of vitamin K‐dependent proteins is the presence of 7‐carboxyglutamyl (Gla) residues formed during the post‐translational processing of these proteins. The energy needed to drive this microsomal carboxylation event comes from the reoxidation of the reduced, hydronaphthoquinone form of vitamin K to its 2,3‐epoxide. Recent studies have suggested that an intermedite epoxide alkoxide is the strong base needed to abstract a proton from the relatively unreactive methylene carbon of the glutamyl residue. The primary gene product of the vitamin K‐dependent proteins contains a homologous propeptide extension between the amino terminus of the mature protein and signal peptide. This region, which is cleaved before secretion of these proteins, serves to dock the protein substrate to the enzyme catalyzing the carboxylation event, and to also alter the apparentKmof the Glu binding site of the enzyme. The order in which the multiple Glu sites on the substrate proteins are carboxylated is unknown, but elucidation of this property of the enzyme and further details of the bioorganic mechanism should be aided by recent reports of purification of this unique carboxylase.— Suttie, J. W. Synthesis of vitamin K‐dependent proteins.FASEB J.7: 445‐452; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.5.8462786

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Ca2+accumulates in the nucleus and DNA undergoes enzymatic cleavage into internucleosomelength fragments before acetaminophen and dimethylnitrosamine produce hepatic necrosis in vivo and toxic cell death in vitro. However, Ca2+‐endonuclease fragmentation of DNA is characteristic of apoptosis, a type of cell death considered biochemically and functionally distinct from toxic cell death. The present studies investigate DNA fragmentation as a critical event in toxic cell death by testing whether the Ca2+‐calmodulin antagonist chlorpromazine and the Ca2+channel blocker verapamil prevent acetaminophen‐induced hepatic necrosis by inhibiting Ca2+deregulation and DNA damage. Acetaminophen overdose in mice produced accumulation of Ca2+in the nucleus (358% of control) and fragmentation of DNA (250% of control) by 6 h, with peak release of ALT occurring at 12–24 h (58,000 U/l). Pretreatment with chlorpromazine prevented increases in nuclear Ca2+and DNA fragmentation and nearly abolished biochemical evidence of toxic cell death. Verapamil pretreatment also decreased Ca2+accumulation and DNA damage while attenuating liver injury. The Ca2+antagonists did not protect against toxic cell death through hypothermia because neither produced the delay in toxicity that is customarily associated with hypothermia. Nor did chlorpromazine or verapamil protect through inhibiting acetaminophen bioactivation. Chlorpromazine failed to diminish glutathione depletion in whole liver and isolated nuclei. Verapamil (250 μM) also failed to alter glutathione depletion in whole liver and had no effect on acetaminophenglutathione adduct formation by mouse liver microsomes and by cultured mouse hepatocytes. Collectively, these results support the hypothesis that Ca2+‐induced DNA fragmentation plays a significant role in cell necrosis produced by acetaminophen and may contribute to toxic cell death caused by other alkylating hepatotoxins.— Ray, S. D., Kamendulis, L. M., Gurule, M. W., Yoridn, R. D., Corcoran, G. B. Ca2+antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen.FASEB J.7: 453‐463; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.5.8462787

出版商:Wiley    

年代:1993

数据来源: WILEY