ISSN:0892-6638    

DOI:10.1096/fasebj.2.15.3192040

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Our understanding of how vitamin D mediates biological responses has entered a new era. It is now clear that the bulk of the biological responses supported by vitamin D occur as a consequence of its metabolism to its daughter metabolite 1α,25‐dihydroxyvitamin D3(a steroid hormone). The fact that 1,25(OH)2D3receptors are ubiquitous in tissue distribution opens the possibility for unforeseen biological functions of the vitamin D endocrine system. For example, 1,25(OH)2D3serves as an immunoregulatory hormone and a differentiation hormone besides its classical role in mineral homeostasis. The avian 1,25(OH)2D3receptor has recently been cloned and shown to be a member of the nuclear transacting receptor family that includes estrogen, progesterone, glucocorticoid, thyroxine (T3), aldosterone, and retinoic acid receptors. We have compiled an extensive number of RNA polymerase II‐transcribed genes that are regulated by 1,25(OH)2D3. Classification of these genes on functional grounds identifies and formulates the several genetic circuits or biochemical systems in which 1,25(OH)2D3plays an essential regulatory role. These systems include genes that govern oncogene and lymphokine expression as well as those involved in mineral homeostasis, vitamin D metabolism, and regulation of a set of replication‐linked genes (c‐myc, c‐myb,and histone H4), which are critical for rapid cellular proliferation. An integrated analysis of the combinations of genetic circuits regulated by 1,25(OH)2D3suggests that they may be collectively tied to a DNA replication‐differentiation switch.— Minghetti, P. P.; Norman, A. W. 1,25(OH)2‐Vitamin D3receptors: gene regulation and genetic circuitry.FASEB J.2: 3043‐3053; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.15.2847948

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Cytogenetic studies are providing clues to the growth regulatory genes involved in human carcinogenesis and to mechanisms that alter their function. Investigations of chromosome translocations in B and T cell lymphomas and in chronic myelogenous leukemia have demonstrated the effects on protooncogenes of transposition within the genome, with or without structural change in the gene. These studies have also provided evidence for many previously unidentified human oncogenes. Similarly, the recognition through cytogenetics of gene amplification units in aggressive forms of certain tumors has helped to define another important type of somatic genetic change in neoplasia, again involving both known and previously unknown oncogenes. The observation of nonrandom chromosomal deletions in other malignancies has contributed to the delineation of an additional major class of tumorigenic genes, called suppressor genes, which appear to have a significant role in inherited malignancies and are now being actively sought in many common cancers. Finally, chromosome studies have helped to demonstrate the clonal nature of most neoplasms and the importance, in tumor progression, of sequential somatic genetic changes within the neoplastic clone. This latter phenomenon appears to depend primarily on acquired genetic lability in the tumor cell population. Karyotypic data are providing leads to its basis, as well as to the significance in carcinogenesis of constitutional chromosomal fragility and of specific fragile sites within the genome of different individuals.— Nowell, P. C.; Croce, C. M. Chromosomal approaches to oncogenes and oncogenesis.FASEB J.2: 3054‐3060; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.15.3056765

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Ion channels in renal epithelia are involved in maintenance of the volume and ion composition of the epithelial cells themselves and of the entire organism. The latter function depends on transepithelial ion transport, a process that often involves ion channels at the apical (luminal) and/or the basolateral (contraluminal) cell membranes. Regulation of these channels is accomplished within many different time frames, each of which can involve different molecular mechanisms of regulation. Changes in membrane voltage, intracellular ion composition, or mechanical force on the membrane mediate short‐term regulation. Biosynthesis, degradation, and reversible transfer of channels to or from cytoplasmic stores are responsible for longer term regulation. Covalent modification of channel proteins can be involved in either short‐ or long‐term regulation. In this review we outline the different models of ion channel regulation in renal epithelia and give examples that emphasize the physiological roles of these channels in specific nephron segments.— Palmer, L. G.; Sackin, H. Regulation of renal ion channels.FASEB J.2: 3061‐3065; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.15.2461326

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Normal skeletal growth results from a balance between the processes of bone matrix synthesis and resorption. These activities are regulated by both systemic and local factors. Bone turnover is dynamic, and skeletal growth must be maintained throughout life. Although many growth promoters are associated with bone matrix, it is enriched particularly with transforming growth factor β (TGF‐β) activity. Experimental evidence indicates that TGF‐β regulates replication and differentiation of mesenchymal precursor cells, chondrocytes, osteoblasts, and osteoclasts. Recent studies further suggest that TGF‐β activity in skeletal tissue may be controlled at multiple levels by other local and systemic agents. Consequently, the intricate mechanisms by which TGF‐β regulates bone formation are likely to be fundamental to understanding the processes of skeletal growth during development, maintenance of bone mass in adult life, and healing subsequent to bone fracture.—Centrella, M.; McCarthy, T. L.; Canalis, E. Skeletal tissue and transforming growth factor 0.FASEB J.2: 3066‐3073; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.15.2903838

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Many cells display oscillations in intracellular calcium resulting from the periodic release of calcium from intracellular reservoirs. Frequencies are varied, but most oscillations have periods ranging from 5 to 60 s. For any given cell, frequency can vary depending on external conditions, particularly the concentration of natural stimuli or calcium. This cytosolic calcium oscillator is particularly sensitive to those stimuli (neurotransmitters, hormones, growth factors) that hydrolyze phosphoinositides to give diacylglycerol and inositol 1,4,5‐trisphosphate (Ins1,4,5P3). The ability of Ins1,4,5P3to mobilize intracellular calcium is a significant feature of many of the proposed models that are used to explain oscillatory activity. Receptor‐controlled oscillator models propose that there are complex feedback mechanisms that generate oscillations in the level of Ins1,4,5P3. Second messenger‐controlled oscillator models demonstrate that the oscillator is a component of the calcium reservoir, which is induced to release calcium by a constant input of either Ins1,4,5P3or calcium itself. In the latter case, the process of calcium‐induced calcium release might be the basis of oscillatory activity in many cell types. The function of calcium oscillations is still unknown. Because oscillator frequency can vary with agonist concentration, calcium transients might be part of a frequency‐encoded signaling system. When an external stimulus arrives at the cell surface the information is translated into a train of calcium spikes, i.e., the signal is digitized. Certain cells may then convey information by varying the frequency of this digital signal.—Berridge, M. J.; Galione, A. Cytosolic calcium oscillators.FASEB J.2: 3074‐3082; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.15.2847949

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Febrile sepsis was induced in rats by repeated s.c. injections of liveEscherichia colibacteria. Glucose utilization of different tissues was investigated in vivo by using the 2‐deoxyglucose tracer technique. In septic rats the rate of glucose utilization was increased in macrophage‐rich tissues, including the liver (2.7‐fold), spleen (2.4‐fold), and ileum (1.6‐fold), compared with tissues from time‐matched nonseptic animals. A smaller increase in glucose utilization was evident in the abdominal muscle (1.3‐fold) and in the white portion of the quadriceps muscle (1.3‐fold). Changes were not significant in nine other tissues, including the brain. We postulate that in sepsis the mononuclear phagocyte system may be responsible for most of the increment of glucose utilization, and the latter provides metabolic support for the increased antibacterial activity of these cells.—Meszaros, K.; Lang, C. H.; Bagby, G. J.; Spitzer, J. J. In vivo glucose utilization by individual tissues during nonlethal hypermetabolic sepsis.FASEB J.2: 3083‐3086; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.15.3056766

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Interleukin 1 (IL 1) inhibits the growth of human melanoma A375 cells (1). To identify the subcellular events preceding inhibition of growth by IL 1, we have examined the effect of IL 1 on protein synthesis caused by A375 cells. IL 1 selectively and predominantly induced a 25‐kDa polypeptide (p25) in A375 cells after 12 h. On subcellular fractionation, p25 was exclusively located in the 10,000 xg‐pelleted (mitochondria‐enriched) fraction. To identify the p25 moiety, it was purified to homogeneity by sequential chromatography on DEAE‐Sephacel and reverse‐phase, high‐pressure liquid chromatography and its amino‐terminal amino acid sequence was determined. The sequence of the 35 amino‐terminal amino acids of the p25 moiety was identical to that of human manganese superoxide dismutase (Mn SOD) (2). The enzymatic activities of SOD were induced only in the mitochondria‐enriched fraction of IL 1‐treated A375 cells. However, IL 1 also induced Mn SOD in normal human skin fibroblasts and peripheral blood mononuclear cells, whose growth was stimulated by IL 1. The results show that induction of Mn SOD by IL 1 is a common biochemical event in IL 1‐responsive cells.—Masuda, A.; Longo, D. L.; Kobayashi, Y.; Appella, E.; Oppenheim, J. J.; Matsushima, K. Induction of mitochondrial manganese superoxide dismutase by interleukin 1.FASEB J.2: 3087‐3091; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.15.3263930

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Uricase is a peroxisomal liver enzyme that catalyzes the oxidation of uric acid to allantoin during purine catabolism. It is present in vertebrates in most species of fish, amphibians, and mammals but its enzymatic activity is absent in hominoids. We have used Western blot analysis in a comparative study to establish a homology among uricases from different species of vertebrates. Using antibodies against denatured rat liver uricase, we have been able to detect for the first time cross‐reactivity with the uricase of species ranging in the evolutionary scale from fish to primates (macaque). Our results suggest that these uricases have a common evolutionary origin. Our conclusion is also supported by the fact that uricase from different species exhibits identical tissue, subcellular localization, and similarity of molecular weights. This study was extended to include human liver samples. Using the same approach but with a more sensitive detection system (alkaline phosphatase instead of peroxidase), we did not detect polypeptide species related to rat uricase in human fetal or adult liver samples, which indicates that during hominoid evolution, the mutational event responsible for the loss of uricase activity in humans precluded formation of a translatable uricase mRNA.— Varela‐Echavarria, A.; MontesdeOca‐Luna, R.; Barrera‐Saldana, H. A. Uricase protein sequences: conserved during vertebrate evolution but absent in humans.FASEB J.2: 3092‐3096; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.15.3192041

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

In this paper we elucidate part of the mechanism of the early stages of the biosynthesis of glycogen. This macromolecule is constructed by covalent apposition of glucose units to a protein, glycogenin, which remains covalently attached to the mature glycogen molecule. We have now isolated, in a 3500‐fold purification, a protein from rabbit muscle that has the sameMras glycogenin, is immunologically similar, and proves to be a self‐glucosylating protein (SGP). When incubated with UDP‐[14C]glucose, an average of one molecular proportion of glucose is incorporated into the protein, which we conclude is the same as glycogenin isolated from native glycogen. The native SGP appears to exist as a high‐molecular‐weight species that contains many identical subunits. Because the glucose that is self‐incorporated can be released almost completely from the acceptor by glycogenolytic enzymes, the indication is that it was added to a preformed chain or chains of 1,4‐linked α‐glucose residues. This implies that SGP already carries an existing maltosaccharide chain or chains to which the glucose is added, rather than glucose being added directly to protein. The putative role of SGP in glycogen synthesis is confirmed by the fact that glucosylated SGP acts as a primer for glycogen synthase and branching enzyme to form high‐molecular‐weight material. SGP itself is completely free from glycogen synthase. The quantity of SGP in muscle is calculated to be about one‐half the amount of glycogenin bound in glycogen.— Lomako, J.; Lomako, W. M.; Whelan, W. J. A self‐glucosylating protein is the primer for rabbit muscle‐glycogen biosynthesis.FASEB J.2: 3097‐3103; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.15.2973423

出版商:Wiley    

年代:1988

数据来源: WILEY