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At least 865 records · Page 48Linked to original sources
PubMed2003

Troglitazone antagonizes tumor necrosis factor-alpha-induced reprogramming of adipocyte gene expression by inhibiting the transcriptional regulatory functions of NF-kappaB.

Troglitazone (TGZ), a member of the thiazolidinedione class of anti-diabetic compounds and a peroxisome proliferator activator receptor-gamma (PPAR-gamma) agonist, restores systemic insulin sensitivity and improves the full insulin resistance syndrome in vivo. The mechanisms underlying its in vivo function are not understood. Here we investigated the potential functional interaction between PPAR-gamma and NF-kappaB in adipocytes. We show that TGZ selectively blocked tumor necrosis factor-alpha-induced and NF-kappaB-dependent repression of multiple adipocyte-specific genes and induction of growth phase and other genes. This occurs without interfering with NF-kappaB expression, activation, nuclear translocation, or DNA binding and without suppressing NF-kappaB-dependent survival signals. Notably, the expressions of some tumor necrosis factor-alpha-induced genes in adipocytes were unaffected by PPAR-gamma activation. In reporter gene assays in HeLa cells, ectopic expression of PPAR-gamma abolished induction of a NF-kappaB-responsive reporter gene by the p65 subunit (RelA) of NF-kappaB, and the inhibition was further enhanced in the presence of TGZ. Conversely, overexpression of p65 inhibited induction of a PPAR-gamma-responsive reporter gene by activated PPAR-gamma in a dose-dependent manner. The inhibitory effect was independent of the presence of NF-kappaB-binding sites in the promoter region. Other NF-kappaB family members, p50 and c-Rel as well as the S276A mutant of p65, blocked PPAR-gamma-mediated gene transcription less effectively. Thus, p65 antagonizes the transcriptional regulatory activity of PPAR-gamma in adipocytes, and PPAR-gamma activation can at least partially override the inhibitory effects of p65 on the expression of key adipocyte genes. Our data suggest that inhibition of NF-kappaB activity is a mechanism by which PPAR-gamma agonists improve insulin sensitivity in vivo and that adipocyte NF-kappaB is a potential therapeutic target for obesity-linked type 2 diabetes.

3T3 Cells↗
PubMed1987

Ultrastructural and autoradiographic observations on multinucleated blastomeres of human cleaving embryos obtained by in-vitro fertilization.

Human embryos from the 2-cell to the morula stage developing in vitro after monospermic fertilization were incubated with [3H]thymidine or [3H]uridine and those possessing multinucleated blastomeres were examined by conventional transmission electron microscopy and by light- and electron-microscope autoradiography. Labelled DNA was present in all nuclei showing normal ultrastructural appearance, in pseudonuclei lacking nucleoli and their precursors and often demonstrating an unusual chromatin organization, free in the cytoplasm in structures resembling aggregates of dense chromatin and in small cytoplasmic vesicles in the close vicinity of these aggregates. The labelling with [3H]thymidine was not detected in about 50% of the cytoplasmic chromatin aggregates, suggesting that this extranuclear DNA was no longer replicated. Signs of extrusion of pseudonuclei to the extracellular space were occasionally observed. RNA synthesis could not be detected on free cytoplasmic chromatin, while [3H]uridine was incorporated into all nuclei and most pseudonuclei of multinucleated blastomeres of embryos at the 8-cell and morula stages. However, the major outburst of transcriptional activity and the ultrastructural cytoplasmic changes typical of the assumption of embryonic genome expression, occurring normally at the 8-cell stage, were observed only exceptionally.

Autoradiography↗
PubMed1981

Purification and characterization of ovine astrovirus.

Astrovirus, purified in aggregated form from epithelial cells of the small intestinal villi of infected gnotobiotic lambs, was shown to have a single-stranded RNA genome with an S value of 34 and poly(A) tract. Only two major capsid polypeptides were detected with similar mol. wt. of approx. 3.3 x 10(4).

Animals↗
PubMed1988

mRNA decay rates in late-developing Dictyostelium discoideum cells are heterogeneous, and cyclic AMP does not act directly to stabilize cell-type-specific mRNAs.

We reevaluated the use of 32PO4 pulse-chases for analyzing mRNA decay rates in late-developing Dictyostelium cells. We found that completely effective PO4 chases could not be obtained in developing cells and that, as a consequence, the decay rates exhibited by some mRNAs were influenced by the rates at which they were transcribed. In developing cells disaggregated in the presence of cyclic AMP, the poly(A)+ mRNA population turned over with an apparent half-life of 4 h, individual mRNA decay rates were heterogeneous, and some prestalk and prespore mRNAs appeared to decay with biphasic kinetics. In cells disaggregated in the absence of cyclic AMP, all prestalk and prespore mRNAs decayed with biphasic kinetics. During the first 1 to 1.5 h after disaggregation in the absence of cyclic AMP, the cell-type-specific mRNAs were selectively degraded, decaying with half-lives of 20 to 30 min; thereafter, the residual prestalk and prespore mRNA molecules decayed at rates that were similar to those measured in the presence of cyclic AMP. This short-term labilization of cell-type-specific mRNAs was observed even for those species not requiring cyclic AMP for their accumulation in developing cells. The observation that cell-type specific mRNAs can decay at similar rates in disaggregated cells with or without cyclic AMP indicates that this compound does not act directly to stabilize prestalk and prespore mRNAs during development and that its primary role in the maintenance of cyclic-AMP-dependent mRNAs is likely to be transcriptional.

Cell Aggregation↗
PubMed2001

Cigarette smoke extract induces endothelin-1 via protein kinase C in pulmonary artery endothelial cells.

We examined the mechanism of endothelin (ET)-1 regulation by cigarette smoke extract (CSE) and the effect of platelets on CSE-induced stimulation of ET-1 gene expression in human and bovine pulmonary artery endothelial cells (PAECs). Our data show that CSE (1%) induces ET-1 gene expression (after 1 h) and ET-1 peptide synthesis (after 4 h) in bovine PAECs. The induction of preproET-1 mRNA level was due to de novo transcription, and new protein synthesis was not required for this induction. The protein kinase C inhibitors staurosporine (10(-8) mol/l) and calphostin C (10(-7) mol/l) abolished the induction of ET-1 gene expression by CSE in bovine and human PAECs. Although a lower concentration of platelets (10(6) cells/ml in bovine PAECs; 10(7) cells/ml in human PAECs) did not significantly alter ET-1 gene expression in PAECs, incubation of platelets with CSE (1%) and PAECs produced a significant increase in preproET-1 mRNA and ET-1 peptide compared with the values in the presence of CSE (1%) alone. CSE (1%) induced platelet aggregation and increased the expression of platelet membrane glycoproteins ex vivo. Thus our data suggest that CSE stimulates ET-1 gene expression via PKC in PAECs. CSE and platelets showed a synergistic effect on ET-1 gene expression, possibly through the activation of platelets by CSE.

Animals↗
PubMed2004

Levels of human Fis1 at the mitochondrial outer membrane regulate mitochondrial morphology.

Mitochondria undergo balanced fission and fusion events that enable their appropriate networking within the cell. In yeast, three factors have been identified that co-ordinate fission events at the mitochondrial outer membrane. Fis1p acts as the outer membrane receptor for recruitment of the dynamin member, Dnm1p and the WD40-repeat-containing protein Mdv1p. In mammals, the Dnm1p counterpart Drp1 has been characterized, but other components have not. Here, we report the characterization of human Fis1 (hFis1). hFis1 is inserted into the mitochondrial outer membrane via a C-terminal transmembrane domain that, along with a short basic segment, is essential for its targeting. Although expression of hFis1 does not complement the phenotype of yeast cells lacking Fis1p, overexpression of hFis1 in tissue culture cells nevertheless causes mitochondrial fragmentation and aggregation. This aggregation could be suppressed by expressing a dominant-negative Drp1 mutant (Drp1(K38A)). Knockdown of hFis1 in COS-7 cells using RNA interference results in mitochondrial morphology defects with notable extensions in the length of mitochondrial tubules. These results indicate that the levels of hFis1 at the mitochondrial surface influences mitochondrial fission events and hence overall mitochondrial morphology within the cell.

Amino Acid Sequence↗
PubMed1993

Cloning of the polyubiquitin cDNA from the marine sponge Geodia cydonium and its preferential expression during reaggregation of cells.

Ubiquitination of proteins is a critical step in the controlled degradation process of many polypeptides. Here we show that sponges, the simplest multicellular group of eukaryotic organisms, are also equipped with the ubiquitin pathway. The polyubiquitin cDNA was isolated and characterized from the marine sponge Geodia cydonium. The open reading frame contains six ubiquitin moieties, which are lined up head to tail without spacers. A comparison of the predicted amino acid sequence of the six sponge ubiquitin-coding units with those from other organisms revealed a high degree of homology (> 93%). The ubiquitin gene is expressed to almost the same extent in the two main compartments of the sponge, the cortex and the medulla. However, only in the cortex are detectable amounts of the ubiquitin protein synthesized. The ubiquitin protein isolated from the sponge organism was found to initiate protein degradation in the heterologous reticulocyte system in the same manner as bovine ubiquitin. In vitro studies with dissociated sponge cells revealed that the homologous aggregation factor causes (i) a strong increase in the steady-state level of mRNA coding for ubiquitin and (ii) a drastic increase in ubiquitin protein synthesis, while the homologous lectin failed to display that effect in isolated cells. These data suggest that ubiquitin may play a role in sponge morphogenesis.

Adenosine Triphosphate↗
PubMed1999

Noggin expression in a mesodermal pluripotent cell line C1 and its regulation by BMP.

Osteoblasts and chondrocytes are derived from mesodermal stem cells and their differentiation is under the control of coordinated interaction among signaling molecules. Noggin is one of the signaling molecules which bind to and inactivate BMPs to induce neural tissues and dorsal mesoderm in Xenopus. However, its expression and regulation in mammalian cells has not been known. In this study, we investigated expression of noggin in murine pluripotent mesodermal cell line, C1. Noggin expression was very low in these C1 cells before they were induced to differentiate. When C1 cells were induced to differentiate into chondrocytes in aggregate cultures in the presence of dexamethasone(dex), noggin expression was significantly increased. In a sharp contrast, when the C1 cells were induced to differentiate into osteoblastic cells by the treatment with beta glycerophosphate (betaGP) and ascorbic acid (AA), noggin mRNA expression remained to be barely detectable. Noggin expression was also observed in the developing cartilage of vertebrae in 15.5 dpc mouse embryos. The noggin mRNA level in C1 cells in monolayer cultures was enhanced significantly by the treatment with BMP4/7 in a dose-dependent manner with a maximal effect at 100 ng/ml. The BMP4/7 effect on noggin expression was time dependent starting within 12 h and peaked at 24 h. These results indicate that noggin is expressed in the pluripotent mesodermal cell line C1 and that its expression is regulated by BMP.

Animals↗
PubMed1993

Myocardial alpha-thrombin receptor activation induces hypertrophy and increases atrial natriuretic factor gene expression.

The protease, alpha-thrombin (alpha Th), affects myocardial cell contractility, a feature common among agents that induce hypertrophy. However, it is not known whether cardiac myocytes possess alpha Th receptors (alpha Th-R), or if long term treatment with alpha Th can enhance growth and gene expression. In the present study primary neonatal rat ventricular myocytes expressed a 3.6-kilobase mRNA species that hybridized with a rat alpha Th-R-specific probe. After 48 h, alpha Th induced hypertrophy, sarcomeric organization, and enhanced atrial natriuretic factor (ANF) expression, all of which were blocked by the alpha Th-selective protease inhibitor, D-Phe-Pro-Arg-chloromethyl ketone. The alpha Th-R agonist peptide, SFLLRNPND, was a potent activator of ANF expression, however, the non-agonist, FLLRNPND, was inactive. Transfection experiments showed the enhancement of ANF expression by alpha Th to be transcriptional. The abilities of alpha Th to induce myocyte hypertrophy and to augment ANF transcription and peptide production were inhibited by the protein kinase C inhibitor, chelerythrine, and by the tyrosine kinase inhibitor, tyrphostin. Thus, myocardial cell alpha Th-Rs are stimulated by the specific proteolytic actions of alpha Th, and pathways involving both protein kinase C and protein tyrosine kinases are required for subsequent hypertrophy and ANF expression. Further, these findings suggest a new role for extracellular proteases as regulators of myocardial cell gene expression and growth.

Alkaloids↗
PubMed1997

Leucocytoclastic vasculitis associated with mixed cryoglobulinaemia and hepatitis C virus infection.

Mixed cryoglobulinaemia is frequently associated with chronic hepatitis. We report a patient with mixed cryoglobulinaemia, hepatitis C virus (HCV) infection and palpable purpura. The skin manifestations were diagnosed as leucocytoclastic vasculitis in view of both the clinical appearance and the histological findings. In this study, we demonstrated the presence of IgG-class anti-HCV-antibody, HCV-RNA and IgA-class rheumatoid factor in the cryoprecipitate. These results suggest that the cryoglobulinaemia in this case was caused by aggregation of an immune complex comprised of HCV and anti-HCV antibody with IgA-type-rheumatoid factor, and that this led to a cutaneous vasculitis.

Antigen-Antibody Complex↗
PubMed1990

Increased gap junction assembly between cultured cells upon cholesterol supplementation.

Novikoff hepatoma cells provide an excellent model system for the study of gap junction assembly, a process that could be influenced by lipids and other factors at numerous points. Since it is possible to alter the cellular levels of cholesterol in these cells, it was added to the cells in serum-supplemented medium and changes in gap junction assembly were evaluated. Cells were dissociated and reaggregated following exposure to a range of cholesterol concentrations for 24 h. A five- to sixfold increase in the number of aggregated gap junction particles and a 50% increase in cellular cholesterol content were observed with 20 microM added cholesterol. A 1-h exposure to added cholesterol, during cell reaggregation, resulted in a fourfold increase in the number of aggregated gap junction particles, demonstrating that the effect was rapid. The number of aggregated gap junction particles and formation plaque areas were used as measures of junction assembly and assayed by quantitative freeze-fracture and electron microscopy. Junctional permeabilities were evaluated by means of dye transfer times following the intracellular microinjection of Lucifer Yellow. Increased dye transfer was observed between cholesterol-treated cells, which suggested that the increase in assembly was accompanied by an increase in junction permeability. Cells were treated with cycloheximide (100 micrograms ml-1) and actinomycin D (10 micrograms ml-1) to determine whether protein and RNA syntheses were involved in the enhanced gap junction assembly. Cycloheximide but not actinomycin D blocked the increased junction assembly observed with added cholesterol. These results suggested that protein synthesis, but not RNA synthesis, is necessary for the increased gap junction formation observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Gene expression (collagenase, tissue inhibitor of metalloproteinases, complement, and HLA-DR) in rheumatoid arthritis and osteoarthritis synovium. Quantitative analysis and effect of intraarticular corticosteroids.

In situ hybridization was used to localize and quantify gene expression in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue. Collagenase, tissue inhibitor of metalloproteinases (TIMP), HLA-DR, and complement (C2 and C3) gene expression was studied in synovial tissue from 23 patients with RA, OA, or other inflammatory arthropathies. Gene expression was highly compartmentalized: Collagenase, TIMP, and C2 messenger RNA (mRNA) were localized primarily to the synovial lining layer; HLA-DR mRNA was prominent in the lining and in some sublining lymphoid aggregates; the C3 probe hybridized only to sublining lymphoid aggregates. Relative mRNA levels were quantified using computer-assisted image analysis. There was significantly more collagenase, C2, C3, and HLA-DR mRNA in RA compared with OA patients. However, TIMP mRNA levels were similar in RA and OA. Expression of collagenase, TIMP, C2, C3, and HLA-DR genes correlated with the degree of synovial inflammation. The effect of intraarticular corticosteroid injection on synovial tissue gene expression was studied using serial percutaneous synovial biopsy samples from the knees of 3 RA patients. Joints were biopsied, injected with triamcinolone, and rebiopsied 1-2 weeks later. Histologic inflammation scores were lower in posttreatment synovia. Collagenase and TIMP mRNA, although abundant in presteroid samples, were nearly undetectable in post-steroid tissues. HLA-DR mRNA levels also were significantly decreased. C2 and C3 hybridization significantly decreased in 2 of 3 patients and 1 of 3 patients, respectively. Hence, clinical response to intraarticular steroid therapy was accompanied by histologic improvement and decreased expression of genes that play a role in articular destruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed2002

Relating whole-genome expression data with protein-protein interactions.

We investigate the relationship of protein-protein interactions with mRNA expression levels, by integrating a variety of data sources for yeast. We focus on known protein complexes that have clearly defined interactions between their subunits. We find that subunits of the same protein complex show significant coexpression, both in terms of similarities of absolute mRNA levels and expression profiles, e.g., we can often see subunits of a complex having correlated patterns of expression over a time course. We classify the yeast protein complexes as either permanent or transient, with permanent ones being maintained through most cellular conditions. We find that, generally, permanent complexes, such as the ribosome and proteasome, have a particularly strong relationship with expression, while transient ones do not. However, we note that several transient complexes, such as the RNA polymerase II holoenzyme and the replication complex, can be subdivided into smaller permanent ones, which do have a strong relationship to gene expression. We also investigated the interactions in aggregated, genome-wide data sets, such as the comprehensive yeast two-hybrid experiments, and found them to have only a weak relationship with gene expression, similar to that of transient complexes. (Further details on genecensus.org/expression/interactions and bioinfo.mbb.yale.edu/expression/interactions.)

Gene Expression Profiling↗
PubMed2026

Reduced CCL/Be-specific CD4+ T cells in CCL3-deficient or peptide-MHCII CAR-T cell-treated mice.

In chronic beryllium disease (CBD), elevated levels of the inflammatory chemokines CCL3 and CCL4 in the lungs coincide with expanded populations of CD4+ T cells specific to beryllium-modified (Be-modified) peptides derived from these chemokines. Here, we generated HLA-DP2 transgenic (Tg) CCL3-deficient mice (CCL3-/-) that also lack CCL4 to investigate their role in disease development. Be-exposed CCL3-/- mice maintained normal numbers of lung macrophages and dendritic cells (DCs) but exhibited significantly reduced total and HLA-DP2-CCL/Be tetramer-specific CD4+ T cells, IFN-γ-producing CD4+ T cells, and peribronchovascular aggregates, consistent with attenuated inflammation. CCL3 was predominantly expressed in macrophages and DCs, and bone marrow chimera studies confirm that hematopoietic-derived DCs are the key regulators of CCL/Be-specific CD4+ T cell responses. RNA-seq of lung-resident CCL4/Be tetramer+ CD4+ T cells revealed a transcriptional profile enriched for inflammatory and cholesterol-metabolism pathways, with elevated expression of Ifng, Tnf, and Il17a. Moreover, Be-exposed HLA-DP2 Tg mice lacking TNF-α or treated with peptide-MHCII CAR-T cells targeting CCL4/Be-specific CD4+ T cells showed reduced T cell responses and cellular aggregates. These findings demonstrate that CCL3 and CCL4 promote CCL/Be-specific CD4+ T cell responses and highlight peptide-MHCII CAR-T cells as a potentially novel strategy for depleting self-peptide/Be-specific CD4+ T cells in CBD.

Animals↗
PubMed2004

Cloning and expression of an acidic platelet aggregation inhibitor phospholipase A2 cDNA from Bothrops jararacussu venom gland.

The phospholipase A2 (PLA2, E.C. 3.1.1.4) superfamily is defined by enzymes that catalyze the hydrolysis of the sn-2 bond of phosphoglycerides. Most PLA2s from the venom of Bothrops species are basic proteins, which have been well characterized both structurally and functionally, however, little is known about acidic PLA2s from this venom. Nevertheless, it has been demonstrated that they are non-toxic, with high catalytic and hypotensive activities and show the ability to inhibit platelet aggregation. To further understand the function of these proteins, we have isolated a cDNA that encodes an acidic PLA2 from a cDNA library prepared from the poly(A)+ RNA of venom gland of Bothrops jararacussu. The full-length nucleotide sequence of 366 base pairs encodes a predicted gene product with 122 amino acid with theoretical isoelectric point and size of 5.28 and 13,685 kDa, respectively. This acidic PLA2 sequence was cloned into expression vector pET11a (+) and expressed as inclusion bodies in Escherichia coli BL21(DE3)pLysS. The N-terminal amino acid sequence of the 14 kDa recombinant protein was determined. The recombinant acidic PLA2 protein was submitted to refolding and to be purified by RP-HPLC chromatography. The structure and function of the recombinant protein was compared to that of the native protein by circular dichroism (CD), enzymatic activity, edema-inducing, and platelet aggregation inhibition activities.

Amino Acid Sequence↗
PubMed2003

Turning teratocarcinoma cells into neurons: rapid differentiation of NT-2 cells in floating spheres.

Cells from the human teratocarcinoma line NTera-2 can be induced to terminally differentiate into postmitotic neurons when treated with retinoic acid. However, this differentiation process is rather time consuming as it takes between 42 and 54 days. Here, we propose a modified differentiation protocol which reduces the time needed for differentiation considerably without compromising the quantity of the neurons obtained. The introduction of a proliferation step as free floating cell spheres cuts the total time needed to obtain high yields of purified NT-2 neurons to about 24-28 days. The cells obtained show neuronal morphology and migrate to form ganglion-like cell conglomerates. Differentiated cells express neuronal polarity markers such as the cytoskeleton associated proteins MAP2 and Tau. Moreover, the generation of neurons in sphere cultures induced immunoreactivity to the ELAV-like neuronal RNA-binding proteins HuC/D, which have been implicated in mechanisms of nerve cell differentiation.

Biomarkers↗
PubMed2004

Modified single-stranded oligonucleotides inhibit aggregate formation and toxicity induced by expanded polyglutamine.

Huntington's disease (HD) is caused by an increase in the length of the poly(Q) tract in the huntingtin (Htt) protein, which changes its solubility and induces aggregation. Aggregation occurs in two general phases, nucleation and elongation, and agents designed to block either phase are being considered as potential therapeutics. We demonstrate that inclusion formation can be retarded by introducing modified, single-stranded oligonucleotides into a model neuronal cell line. This cell-based assay is used in conjunction with a standardized biochemical assay to identify molecules that can disrupt the process of aggregate formation. Active oligonucleotides include a 6-mer containing a single phosphorothioate linkage on each terminus, a 53-mer and a 9-mer containing three phosphorothioate linkages at each end, and a 25-mer consisting of all modified RNA residues. The disruption process directed by the active oligonucleotides appears to be independent of sequence specificity and complementarity. In contrast, the activity is more dependent on the type of chemical modifications contained within the oligonucleotide. Some oligonucleotides that demonstrated inhibition activity were also found to extend the life span of PC12 cells after the toxic Htt aggregation process was induced. Our data provide the first evidence that short synthetic oligonucleotides inhibit a fundamental pathological pathway of HD and may provide the basis for a novel therapeutic approach.

Animals↗
PubMed1983

Histidase mRNA. Nature of translational products, tissue specificity, and differential development in male and female rat liver.

Histidase is expressed in only two tissues of the rat, liver and epidermis. Hepatic histidase synthesis and catalytic activity undergo complex sex-specific developmental courses. To determine whether changes in functional histidase mRNA levels underlie this developmental pattern, total cellular RNA was translated in a rabbit reticulocyte cell-free lysate system. Adult liver total cellular RNA directed the synthesis of three translational products immunoreactive with anti-native histidase: a polypeptide of Mr = 75,000 (75K), which corresponds to the in vivo synthesized histidase subunit, and two higher molecular weight proteins, a major and a minor peptide of Mr = 150,000 (150K) and 140,000 (140K), respectively. These latter peptides do not seem to be aggregates or dimers of the 75K polypeptide or precursors which are post-translationally hydrolyzed to Mr = 75,000; their origin and function remain to be clarified. In contrast to in vitro translation of hepatic total cellular RNA, Western blot analysis of liver cytosol confirms the presence of only the 75K histidase subunit, with no evidence of anti-histidase immunoreactive peptides of Mr = 140,000-150,000 synthesized in vivo. Quantitation of the radioactivity in the immunocomplexed 75K histidase subunit, translated using total RNA from livers of fetuses, 19-day-old males, 35-day-old males, adult males and females, and adult kidney and brain (0, 0.007, 0.010, 0.016, 0.031, 0, and 0%, respectively, of total released proteins) indicates that, in general, levels of functional histidase subunit mRNA reflected histidase catalytic activity (0, 0.20, 0.50, 1.01, 3.00, 0 and 0 units/g of tissue) during tissue differentiation and sex specific development. The above data indicate that initial expression and subsequent increases in synthesis and activity of histidase during hepatic differentiation, postnatal development, and sex hormone regulation are due to pretranslationally controlled augmentation in the levels of functional mRNA which specifies the histidase subunit. In tissues which do not express histidase no functional histidase mRNA is evident. The levels of the RNA which translate the combined 140-150K histidase-like polypeptides (0, 0.007, 0.014, 0.035, 0.034, 0, and 0% of released proteins) also paralleled the increase in enzymatic activity during tissue differentiation and development; however, no difference between males and females was evident. The significance of these observations awaits elucidation of the nature of these RNA(s).

Ammonia-Lyases↗