摘要:

The ATP‐Mg/Picarrier in liver mitochondria can catalyze the exchange of ATP‐Mg on one side of the inner membrane for Pion the other. This mechanism allows for net uptake or release of ATP‐Mg from mitochondria and thus regulates the matrix ATP + ADP + AMP pool size. In isolated mitochondria, carrier activity is stimulated by submicromolar concentrations of calcium, suggesting that calcium may regulate transport rates in vivo. Whenever the carrier is active, the direction of any net changes in the matrix adenine nucleotide pool size is determined mainly by the extent to which the prevailing ATP‐Mg concentration gradient deviates from an equilibrium related to Δ pH through the phosphate concentration gradient. Thus it seems that in the cell, energy status (reflected by ATP:ADP ratios in the cytoplasm and matrix) determines whether calcium‐mediated hormone activation of the carrier will produce an increase or a decrease in the matrix adenine nucleotide content. Consequent variations in the absolute concentrations of ATP, ADP, and AMP in the matrix may contribute to the selective regulation of those metabolic activities in the cell that have adenine nucleotide dependent steps localized to the mitochondrial compartment (gluconeogenesis, urea synthesis, mitochondrial biogenesis, and even oxidative phosphorylation).—Aprille,j. R. Regulation of the mitochondrial adenine nucleotide pool size in liver: mechanism and metabolic role.FASEB J.2: 2547‐2556; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.10.3290024

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

In biological systems oxidation of heme is carried out by two isozymes of the microsomal heme oxygenase, HO‐1 and HO‐2. HO‐1 is the commonly known heme oxygenase, the activity of which can be induced by up to 100‐fold in response to a wide variety of stimuli (metals, heme, hormones, etc.). HO‐2 was only recently discovered, and the isozyme appears to be uninducible. The two forms are products of two different genes and differ in their tissue expression. The primary structure of HO‐1 and an HO‐2 fragment of 91 amino acid residues show only 58% homology, but share a region with 100% secondary structure homology. This region is believed to be the catalytic site. Most likely, HO‐1 gene is regulated in the same manner as metallothione in the gene. HO‐1 has a heat shock regulatory element, and possibly many promoter elements, which bind to respective inducers and cause transcription of the gene. In vivo induction of HO‐1 activity in the liver is accompanied by decreases in the total P‐450 levels and, in a reconstituted system, cytochrome P‐450bheme can be quantitatively converted to biliverdin by HO‐1 and HO‐2. The enzyme activity is inhibited in vivo for extended periods subsequent to binding of Zn‐and Sn‐ protoporphyrins. This property appears useful for the suppression of bilirubin production. The metalloporphyrins, however, are not innocuous and cause major disruptions in cellular metabolism. In this review recent findings on heme oxygenase are highlighted.— Maines, M. D. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications.FASEB J.2: 2557‐2568; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.10.3290025

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Guanine nudeotide‐binding regulatory proteins similar to Gsand Gimay be involved in the activation of phospholipases C and A2by hormones and other ligands. The binding of hormones to receptors that activate phospholipase C is decreased by guanine nucleotides and these hormones also stimulate a high‐affinity GTPase activity in cell membranes. Effects of hormones on phospholipase C activity in cell‐free preparations are dependent on the presence of guanine nucleotides. In addition, fluoride and nonhydrolyzable GTP analogs activate phospholipases in a manner that can be blocked by GDPβS. The putative guanine nucleotide‐binding regulatory protein that appears to be involved in activation of phospholipase C is sensitive to pertussis toxin in some cells but not in others.— Fain, J. N.; Wallace, M. A.; Wojcikiewigz, R. J. H. Evidence for involvement of guanine nucleotide‐binding regulatory proteins in the activation of phospholipases by hormones.FASEB J, 2: 2569‐2574; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.10.2838362

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Advances in understanding the phosphoinositide cycle have helped unravel the chain of events initiated by muscarinic receptor stimulation. Hydrolysis of membrane phosphoinositides generates both diacylglycerol, an activator of protein kinase C, and inositol phosphates. In the nervous system, muscarinic receptors elicit a wide range of electrophysiological responses. Recent studies have made progress in identifying which of these neuronal muscarinic actions are mediated by activation of protein kinase C. Paradoxically, protein kinase C also exerts a strong inhibitory influence on muscarinic responses. This complex set of actions suggests that in addition to mediating certain muscarinic responses, protein kinase C also blocks signal transduction as part of a feedback mechanism.— ∗∗∗ElFakahany, E. E.; Alger, B. E.; Lai, W. S.; Pitler, T. A.; Worley, P. F.; Baraban, J. M. Neuronal muscarinic responses: role of protein kinase C.FASEB J.2: 2575‐2583; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.10.2838363

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Cell adhesion or conjugate formation between T lymphocytes and other cells is an important early step in the generation of the immune response. Although the antigen‐specific T cell receptor confers antigen recognition and specificity, a number of other molecules expressed on the T cell surface are involved in the regulation of lymphocyte adhesion. T cell molecules that function to strengthen adhesion include lymphocyte function‐associated antigen (LFA)‐1, CD2, CD4, and CD8. Their ligands have recently been identified. LFA‐1 is a member of the integrin family of adhesion receptors and one of its ligands is intercellular adhesion molecule‐1 (ICAM‐1); a ligand for CD2 is LFA‐3; and ligands for CD4 and CD8 appear to be major histocompatibility complex class II and class I molecules, respectively. In addition, T cells express a number of receptors thought to be involved in cell matrix adhesion. The function and significance of these T cell adhesion receptors and their ligands are reviewed.—Bierer, B. E.; Burakoff, S. J. T cell adhesion molecules.FASEBJ.2: 2584‐2590; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.10.2838364

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Oxidative modification ofEscherichia coliglutamine synthetase renders the enzyme susceptible to proteolytic degradation by a specific protease purified from the bacterium; native enzyme is not a substrate for the protease. A model oxidizing system consisting of ascorbate, iron, and oxygen was used to generate a series of glutamine synthetases of increasing oxidative modification. We assessed the effect of oxidative modification on the surface hydrophobicity of the glutamine synthetases, utilizing hydrophobic chromatography on a phenyl matrix. Initial exposure to the oxidizing system caused inactivation of the enzyme and generated a protein that was more hydrophilic than the native form; it was not a substrate for the protease. Continued exposure to the oxidizing system yielded a protein with additional oxidative modification. This form was distinctly more hydrophobic than the native form and it was very susceptible to proteolytic attack by the purified protease. Thus, oxidative modification modulates the surface hydrophobicity of glutamine synthetase, and this modulation can control susceptibility to proteolysis.— Cervera, J.; Levine, R. L. Modulation of the hydrophobicity of glutamine synthetase by mixed function oxidation.FASEB J.2: 2591‐2595; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.10.2898411

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

We describe a system in which proliferating human breast cancer cells are monitored by NMR spectroscopy for at least 6 days in basement membrane gel (BMG)1threads. The cells are perfused under standard sterile cell culture conditions.31P‐NMR spectra obtained continuously for up to 64 h showed an increase in the signals owing to an increasing number of cells. Cell division in the BMG is easily observed by microscope or by the human eye as the gel opacifies. Spectra of cells in the BMG threads at 20% confluency show a more rapid signal increase than at 60% confluency. Cells grown in vivo in nude mice show a spectrum markedly similar to in vitro spectra in BMG threads, whereas the same cells in agarose threads lack peaks owing to Pi, glycerophosphocholine, and glycerophos‐phoethanolamine. With the high resolution obtained from this system we distinguished intracellular from extracellular Piin vitro, and found that the intracellular pH is equal to that observed in the same cell line in vivo. This cell‐BMG system is in effect a model tumor, but it is composed of a homogeneous cell population that can be observed indefinitely as the cells reproduce. The material needed is inexpensive, the technique is simple and efficient, and no adaptation of the spectrometer is required. This model will be useful for studying intracellular metabolism and the interaction of cells with the basement membrane.— Daly, P. F.; Lyon, R. C.; Straka, E. J.; Cohen, J. S.31P‐NMR spectroscopy of human cancer cells proliferating in a basement membrane gel.FASEB J.2: 2596‐2604; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.10.3384239

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

An increased airway response to various bronchocon‐stricting agents is one of the hallmarks of asthma. An interdependence of heredity and environment appears to determine this nonspecific hyperreactivity of the airways. The present study describes the patterns of inheritance of the airway response to a direct mediator of smooth muscle contraction (acetylcholine) in A/J and C3H/HeJ inbred mice and their offspring. The mean airway response to acetylcholine was greater than sixfold higher in A/J mice as compared with C3H/HeJ mice. Two phenotypes were easily distinguished on the basis of airway responses to acetylcholine in the progeny of A/J and C3H/HeJ mice. These two phenotypes were termed HYPERREACTIVE (after the A/J strain) and HYPOREACTIVE (after the C3H/HeJ strain). The observed frequencies of HYPERREACTIVE and HYPOREACTIVE phenotypes in the (A/J × C3H/HeJ) Fl; (C3H/HeJ × A/J) F1 × C3H/HeJ (C3H/HeJ backcross); and the [(A/J × C3H/HeJ) F1 × (C3H/HeJ x A/J) F1] F2 are consistent with a single autosomal recessive gene primarily controlling acetylcholine‐mediated airway responses. This single gene difference in airway response is completely inhibited by atropine and therefore mediated entirely by the muscarinic acetylcholine receptor.— Levitt, R. C.; Mitzner, W. Expression of airway hyperreactivity to acetylcholine as a simple autosomal recessive trait in mice.FASEB J.2: 2605‐2608; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.10.3384240

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Weanling mice were fed ad libitum from age 23 to 37 days either an 18 or an 0.6% protein diet. Half the animals in each dietary group received supplemental triiodothyronine (T3, 0.2 mg/kg diet). T3increased the primary in vivo antibody response of protein‐deficient mice to sheep red blood cells, as measured by both splenic plaque‐forming cells (PFC) per 106nucleated spleen cells and serum hemagglutinin titers. T3also increased PFC/spleen in well‐nourished mice. The effect on protein‐deficient animals was achieved although nutritional status in these animals, as estimated by weight loss and carcass composition, was further impaired by T3supplementation. These results support the hypothesis that immune functions can be improved independendy of nutritional status in severe (wasting) malnutrition. Insofar as T3was effective in a model of malnutrition that does not reduce serum total or free T3levels, the phenomenon appears to represent a pharmacological action of the hormone.—Perry, K. J.; Filteau, S. M.; Woodward, B. Dissociation of immune capacity from nutritional status by triiodothyronine supplements in severe protein deficiency.FASEB J.2: 2609‐2612; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.10.3290026

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Cultures of vascular smooth muscle cells superfused with [14C]arachidonic acid synthesized the antiplatelet substance prostacyclin as the major cyclooxygenase product. Prostacyclin synthesis was inactivated by aspirin, which irreversibly acetylates cyclooxygenase. Aspirin‐treated cells recovered within 2 h by a process that was blocked by cycloheximide but not by actinomycin D, and that required a serum component identified as epidermal growth factor (EGF). EGF‐induced recovery of cyclooxygenase was greatly potentiated by typeβtransforming growth factor (TGF‐β). Incubation with EGF and TGF‐β in the 0.1‐1.0 nanomolar range stimulated cyclooxygenase recovery up to 20‐fold without increasing [35S]methionine incorporation into other cell proteins. Induction of cyclooxygenase by EGF and TGF‐β also was prevented by cycloheximide but not by actinomycin D. EGF‐dependent recovery was blocked by preincubation with dexamethasone (2 μM), an effect that was duplicated by pure lipocortin (2‐4 μg/ml). Incubation of membrane preparations from these cells with EGF selectively activated phosphorylation of a 35‐kDa cellular protein that comigrated with lipocortin. The results suggest that cyclooxygenase recovery in aspirin‐inactivated vascular smooth muscle cells is mediated by an EGF‐dependent translational control that is inhibited by corticosteroids. The findings also provide a new mechanism whereby corticosteroids suppress inflammatory prostaglandins.— Pash, J. M.; Bailey, J. M. Inhibition by corticosteroids of epidermal growth factor‐induced recovery of cyclooxygenase after aspirin inactivation.FASEB J.2: 2613‐2618; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.10.2968288

出版商:Wiley    

年代:1988

数据来源: WILEY