ISSN:0892-6638    

DOI:10.1096/fasebj.5.2.2004661

出版商:Wiley    

年代:1991

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.5.2.2004662

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

An account is presented of the recent discovery of a pathway of growth by bacteria in which CO or CO2and H2are sources of carbon and energy. The Calvin cycle and subsequently other cycles were discovered in the 1950s, and in each the initial reaction of CO2involved adding CO2to an organic compound formed during the cyclic pathway (for example, CO2and ribulose diphosphate). Studies were initiated in the 1950s with the thermophylic anaerobic organismClostridium thermoaccticum, which Barker and Kamen had found fixed CO2in both carbons of acetate during fermentation of glucose. The pathway of acetyl‐CoA biosynthesis differs from all others in that two CO2are combined with coenzyme A (CoASH) forming acetyl CoA, which then serves as the source of carbon for growth. This mechanism is designated the acetyl CoA pathway and some have called it the Wood pathway. A unique feature is the role of the enzyme carbon monoxide dehydrogenase (CODH), which catalyzes the conversion of CoASH, CO, and a methyl group to acetyl CoA, the final step of the pathway. The pathway involves the reduction of CO2to formate, which then combines with tetrahydrofolate (THF) to form formyl THF. It in turn is reduced to CH3‐THF. The methyl is then transferred to the cobalt on a corrinoid‐containing enzyme. From there the methyl is transferred to CODH, and CO and CoASH bind with the enzyme at separate sites. Acetyl CoA is then synthesized. CODH would more properly be called carbon monoxide dehydrogenase‐acetyl CoA synthase as it catalyzes oxidation of CO to CO2and the synthesis of acetyl CoA. The solution of the mechanism of this pathway required more than 30 years, in part because the intermediate compounds are bound to enzymes, the enzymes are extremely sensitive to O2and must be isolated under strictly anerobic conditions, and the role of a corrinoid and CODH was unprecedented. It is now apparent that this pathway occurs (perhaps with some modification) in many bacteria including the methane and sulfur bacteria. In some humans this pathway is catalyzed by the bacteria of the gut and acetate is produced rather than methane; it is calculated that 2.3 × 106metric tons of acetate are formed daily from CO2. A similar synthesis occurs in the hind gut of termites. It is becoming apparent that the acetyl CoA pathway plays a significant role in the carbon cycle. The direct combination of two CO2to form acetate may have been used by the earliest forms of life rather than the more complicated cyclic mechanisms of autotrophism.—Wood, H. G. Life with CO or CO2and H2as a source of carbon and energy.FASEB J.5: 156–163; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.2.1900793

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Research on voltage‐gated K+channels of the mammalian brain has seen a flood of new data in the last 2 years. A genetic approach, based on theShakermutation ofDrosophila, led to cDNA clones for mammalian voltage‐gated K+channels. K+channel proteins were detected independently and purified with the help of channel specific toxins. From these studies the structure of two families of mammalian K+channels emerged. One family is defined molecularly by the sequence homology of its members, the other by binding sites for the snake toxin dendrotoxin. The two families have several members in common. The voltage‐gated K+channels of mammalian brain are oligomers of glycosilated peptides of 65–95 kDa. The primary structure of these subunits is characterized by six to eight potential transmembrane regions, including the S4 region, the voltage‐sensor of the channels. Associated with at least some K+channels are 38‐ and 42‐kDa peptides of unknown function. The channels give rise to non‐ or slow‐inactivating K+currents that are regulated through phosphorylation by both cAMP‐dependent and an endogenous kinase.—Rehm, H.; Tempel, B. L. Voltage‐gated K+channels of the mammalian brain.FASEB J.5: 164–170; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.2.2004663

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Different helper T cell subsets secrete different patterns of cytokines when stimulated by antigen. The TH1 and TH2 subsets differ in the secretion of at least eight cytokines, and three or more other cytokine secretion patterns also exist among both mouse and human T cell clones. Several properties of strong immune responses suggest that at least the TH1 and TH2 phenotypes can be present in vivo. As cytokines are major determinants of the functions of the T cells that produce them, these patterns lead to different properties of the T cell subsets. TH1 cells mediate several functions connected with cytotoxicity and local inflammatory reactions, and so these T cells are particularly effective at combating viruses and intracellular bacteria and parasites. TH2 cells are much more effective at stimulating B cells to produce antibody, and so should be more effective against free‐living bacteria, and in inducing protective humoral immunity. Antibody and delayed inflammatory reactions are often mutually exclusive during immune responses, and this can be at least partially explained by cross‐inhibition of TH1 and TH2 cells. A newly discovered cytokine, IL10, has been implicated as one of the cross‐regulatory cytokines, as this TH2 product inhibits cytokine synthesis by TH1 cells.—Street, N. E.; Mosmann, T. R. Functional diversity of T lymphocytes due to secretion of different cytokine patterns.FASEB J.5: 171–177; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.2.1825981

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

The cloning, sequencing, and functional expression in host cells of a variety of receptors has led to a focus on the structural determinants of pharmacologic receptors involved in the complex processes of ligand binding and cell activation. The three basic mechanisms of receptor‐mediated transmembrane signaling (ligand‐regulated ion flux; ligand‐regulated receptor‐enzymes; ligand‐regulated receptor‐G protein activation) can now be placed in the structural context of at least three receptor superfamilies:1) ligand‐regulated oligomeric ion channels,2) ligand‐regulated tyrosine kinases, and3) G protein‐linked rhodopsin‐related receptors. For each of these receptor superfamilies, structure‐activity studies that use1) site‐directed mutagenesis,2) cassette switching to form receptor chimeras, and3) sequence‐specific antireceptor antibodies are beginning to delineate the domains responsible for specific receptor functions. Analyses of such receptor domains related to:1) ligand binding,2) membrane insertion,3) catalytic activity (in the case of receptor‐enzymes),4) internalization and interaction with other membrane constituents,5) substrate or G protein binding, and6) regulatory sites of receptor phosphorylation are discussed, using as principal examples the nicotinic receptor for acetylcholine, the epidermal growth factor‐urogastrone receptor, and theβ‐adrenergic receptor. These studies illustrate that in terms of structure‐activity studies, which have traditionally emphasized the ligand, it is now the receptor's turn for intense attention.— Hollenberg, M. D. Structure‐activity relationships for transmembrane signaling: the receptor's turn.FASEB J.5: 178–186; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.2.1848518

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Mouse macrophages and macrophage cell lines such as P388D1or J774 carry at least two distinct Fcγ receptors (FcγR): one specific for the Fc portion of IgG2a (Fcγ2aR, also classified as FcγRI) and another for IgG2b (Fcγ2bR, also classified as FcγRIIβ). These FcγRs should transmit, upon binding of an appropriate ligand, a specific signal that leads to the regulation of macrophage functions, as the interaction of immune complex with cell surface receptor has been shown to lead to suppression of the humoral immune response or B cell differentiation, to the destruction of target cells by antibody‐dependent cell‐mediated cytotoxicity, to activation of arachidonic acid metabolic cascade, to the phagocytosis of opsonized particles, or to the generation of superoxide anion. In this review, we first describe evidence that Fcγ2aR and Fcγ2bR are associated with casein kinase II and phospholipase A2activity, respectively. We will then discuss a potential role for these enzymatic activities in signal transduction pathways that leads to the activation of the arachidonic acid metabolic cascade and adenylate cyclase, to the regulation of phagocytosis, and to the suppression of interferon‐γ action to induce la antigens.—Suzuki, T. Signal transduction mechanisms through Fcγ receptors on the mouse macrophage surface.FASEB J.5: 187–193; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.2.1706281

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

The goal of these experiments was to identify and characterize binding sites in the rat hypothalamus for the peptide, pituitary adenylate cyclase activating polypeptide (PACAP). The 27 amino acid form of PACAP (PACAP27) was used as the radiolabeled ligand in these experiments. Binding of [125I]PACAP27 to hypothalamic membrane preparations was rapid, reversible on addition of unlabeled peptide, and at least partially regulated by GTP. Nonhydrolyzable GTP analogs, guanosine‐5'‐O‐(3‐thiotriphosphate) (GTPγS), guanosine‐5‐(2‐thiodiphosphate) (GDPβS), and guanylylimidophosphate (GppNHp) also displaced [125I]PACAP27 binding to hypothalamic membrane preparations in a dose‐dependent manner. The order of potency for the three analogs was GTPγS>GDPβS>GppNHp. Both forms of the peptide, PACAP27 and PACAP38, were highly potent in displacing bound [125I]PACAP27, whereas VIP or PACAP(1–23) were unable to displace binding at concentrations of up to 500 nM. Scatchard analysis of the PACAP27 and PACAP38 displacement curves revealed that the fit of both curves was consistent with a single class of high‐affinity binding sites, although the site exhibited a greater affinity for PACAP38 compared with PACAP27 (PACAP27Kd= 1452 ± 59 pM; PACAP38Kd= 175 ± 13 pM; Bmax23.2 ± 1.1 pmol/mg protein). The possibility of the existence of a class of binding sites with extremely low affinity cannot be discounted. After covalent cross‐linking of [125I]PACAP27 with its receptor, the molecular weights of the complexes were estimated by electrophoresis and autoradiography. A major band of 60Kdwas evident when membranes were incubated with VIP or PACAP(1–23). Previous incubation with unlabeled PACAP27 or PACAP38 eliminated visualization of this band. These results suggest that a specific, high‐affinity binding site for PACAP27 is present in rat hypothalamus, and that this site shows a greater affinity for PACAP38 compared with PACAP27. The molecular weight of the peptide‐receptor complex is 60,000 kDa, and therefore the receptor itself has an apparent molecular weight 57,000.—Gottschall, P. E.; Tatsuno, I.; Arimua, A. Hypothalamic binding sites for pituitary adenylate cyclcase activating polypeptide: characterization and molecular identification.FASEB J.5: 194–199; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.2.1848519

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Induction of mitosis by certain growth factors is inhibited by pertussis toxin, indicating that the GTP‐binding protein, Gi, is involved in receptor signal transduction to initiate cell division. However, the substrates of receptor‐activated Githat are involved in mitosis have not been determined. The present study has examined whether Gimay directly modulate cell division by receptor‐induced subcellular translocation of the α subunit of Gi(Giα). Insulin and EGF, particularly when added together or in combination with phorbol dibutyrate (PdBu), induced a rapid (1–4 h) redistribution of Giαfrom the plasma membrane to perinuclear sites in the cell. After 2 days of stimulation, Giαhad translocated into the nucleus of dividing cells and bound specifically to the separating chromatin of dividing nuclei. Unstimulated cells did not display translocation of Giα. This demonstrates a direct involvement of Giαin cell division, which provides an apparently uninterrupted link from growth factor receptor to nucleus.—Crouch, M. F. Growth factor‐induced cell division is paralleled by translocation of Giαto the nucleus.FASEB J.5: 200–206; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.2.1900794

出版商:Wiley    

年代:1991

数据来源: WILEY

摘要:

Reperfusion of ischemic tissues causes a paradoxical injury. Here, we measured lactate dehydrogenase (LDH) release as an indicator of tissue damage in perfused rat livers during anoxia and reoxygenation. During anoxia, LDH release was substantially reduced at acidotic pH (pH 6.1–6.9). Using anoxia at pH 6.1 followed by reoxygenation at pH 7.3 to model ischemia and reperfusion, an abrupt release of LDH occurred after reperfusion. A similar release of LDH occurred when pH of anoxic livers was increased to 7.3 without reoxygenation, but LDH release did not occur after reoxygenation at pH 6.1. Thus, a rapid increase of pH rather than reoxygenation accounted for tissue injury after reperfusion of ischemic liver.—Currin, R. T.; Gores, G. J.; Thurman, R. G.; Lemasters, J. J. Protection by acidotic pH against anoxic cell killing in perfused rat liver: evidence for a pH paradox.FASEB J.5: 207–210; 1991.

ISSN:0892-6638    

DOI:10.1096/fasebj.5.2.2004664

出版商:Wiley    

年代:1991

数据来源: WILEY