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At least 19 recordsLinked to original sources

PubMed1975

On the regulation of cyclic AMP level in bacteria. II. In vitro regulation of adenylate cyclase activity. Solubilization and reconstitution of a functional membrane-bound adenylate cyclase system responsive to regulation by glucose.

1. The in vitro regulation of the membrane bound adenylate cyclase of Escherichia coli B/r by a variety of carbohydrates and one mammalian hormone was examined. 2. The membrane bound adenylate cyclase was found responsive to regulation by the various growth substrates and to glucagon. 3. Solubilization of the bacterial membrane preparation by a procedure specific for the solubilization of the phosphotransferase enzyme E1 1 to its E1 1 A and E1 1 B subunits was found to be accompanied by the loss of the adenylate cyclase regulation by glucose. 4. Reconstitution of the membrane was found to result in a recovery of the regulative response of the adenylate cyclase to glucose. 5. A model for the intermediate steps in the interaction between glucose and phosphotransferase E1 1 and the adenylate cyclase is discussed.

Adenylyl Cyclases↗

PubMed1979

Regulation of protein synthesis in reticulocyte lysates: immune serum inhibits heme-regulated protein kinase activity and differentiates heme-regulated protein kinase from double-stranded RNA-induced protein kinase.

A specific immune serum to the heme-regulated inhibitor (HRI) has been prepared by immunizing chickens with highly purified reversible HRI prepared from rabbit reticulocyte lysates. Studies with this immune serum demonstrate that the behavior of purified reversible HRI is similar to that of the inhibitor activated in rabbit reticulocyte lysates: the immune serum (i) inhibits the phosphorylation of the small subunit (38,000 daltons) of the eukaryotic initiation factor eIF-2 by both crude and purified inhibitor preparations; (ii) prevents the concomitant inhibition of protein synthesis by both crude and purified inhibitor preparations; and (iii) prevents the autophosphorylation of the 95,000-dalton polypeptide in purified and crude HRI preparations. The protein kinase and inhibitory activities of crude and partially purified preparations of the double-stranded RNA-induced inhibitor of protein synthesis are not affected by the immune serum prepared to reversible HRI. These results indicate that the inhibitor induced by double-stranded RNA is antigenically distinct from the reversible HRI.

Animals↗

PubMed1979

Posttranscriptional regulation of glucocorticoid-regulated functions.

Relying heavily on studies of TAT regulation in cultured rat hepatoma cell lines, we have attempted in this brief review to discuss possible mechanisms for posttranscriptional regulation of glucocorticoid-sensitive enzymes and to chronicle the evidence for and against posttranscriptional mechanisms for specific enzyme induction by glucocorticoids. Initially, mechanisms were considered that would reconcile results showing sensitivity of both induction and deinduction of TAT to inhibitors of RNA synthesis with studies demonstrating first that glucocorticoids regulate the rates of specific enzyme synthesis and, then, that glucocorticoids regulate levels of enzyme-specific mRNA. Such reconciliation proved unnecessary when it was demonstrated that inhibitors of RNA synthesis such as actinomycin D were not specific for RNA synthesis, but also had effects on mRNA turnover and protein metabolism. The bulk of evidence to date establishes that glucocorticoids promote the production of enzyme-specific mRNA for the proteins whose synthesis is regulated by thses steroids. Nevertheless, there is still very little direct evidence that steroids can modulate rates of specific gene transcription. The glucocorticoid stimulation of mouse mammary tumor virus RNA production in cultured cell lines is the only example to date where such a mechanism is supported by RNA-DNA hybridization studies. Posttranscriptional actions of steroids on the turnover, processing, or extranuclear transport of specific mRNA precursors remain potential steps at which glucocorticoids might function. The rapid turnover of some glucocorticoid-regulated enzymes and their mRNAs not only ensures a rapid response to steroid addition or withdrawal, but also subjects these proteins to relatively large fluctuations upon alterations in overall protein or mRNA metabolism. Thus many of the inductions and repressions of hepatic TAT and TO by mediators other than the glucocorticoids may be attributable entirely to nonspecific mechanisms.

Animals↗

PubMed2025

Identification of gene targets regulated by the IclR-like regulator SL1344_3500 in Salmonella Typhimurium.

Transcriptional regulation of metabolic operons is important for optimal carbohydrate use and for mitigating the accumulation of toxic intermediates. Here, we characterize SL1344_3500, encoding a putative IclR-like regulator in Salmonella enterica Typhimurium. We present genetic and transcriptional evidence that it regulates the expression of two neighboring operons, one designated here as xynABC, enables utilization of xylonate as a sole carbon source. Furthermore, our findings indicate that SL1344_3500 is important for luminal growth in several mouse models, exerting its effects through the suppression of the xynABC operon. Based on the observation that the ΔSL1344_3500 deletion can be stably complemented in vivo, we developed a plasmid stabilization strategy. This gene complementation approach shows promise for generating stable gene reporters for long-term colonization experiments.IMPORTANCEUnderstanding transcriptional regulation in Salmonella enterica Typhimurium is crucial for revealing how enteric pathogens optimize metabolism to compete with commensals in the gut. SL1344_3500, an IclR-like transcriptional regulator controlling genes linked to sugar acid metabolism, is essential for luminal growth in mouse models through gene suppression and represents a potential target for antimicrobial development. Based on these observations, we developed stable reporter plasmids that use gene complementation of SL1344_3500 to prevent plasmid loss during long-term in vivo studies.

Salmonella typhimurium↗

PubMed1979

Between-ovary interaction in the regulation of follicle growth, corpus luteum function, and gonadotropin secretion in the primate ovarian cycle. III. Temporal and spatial dissociation of folliculogenesis and negative feedback regulation of tonic gonadotropin release after luteectomy in rhesus monkeys.

This study was designed to examine effects of previous ovarian status on subsequent follicle growth and the role of between-ovary communication in the regulation of folliculogenesis and gonadotropin secretion during the primate ovarian cycle. Responses to luteectomy were compared in two groups of rhesus monkeys. In the first, follicle growth and corpus luteum function had been constrained chronically to a single ovary by hemiovariectomy performed 66--258 days earlier; the second group was composed of intact monkeys that underwent contralateral wedge resection at luteectomy. In each group, luteal ablation was followed by a prompt fall in serum progesterone levels, a premature onset of menses, and the next preovulatory gonadotropin surges 14.7 +/- 1.1 or 15.4 +/- 1.4 days later (mean +/- SE; P greater than 0.25). Although the patterns of circulating estradiol before and after ablation in each group were superimposable, luteectomy in monkeys lacking a contralateral ovary was followed by a large (2- to 4-fold) and prolonged (7--10 days) increase in serum FSH, whereas in monkeys with two ovaries, serum FSH levels exhibited only a small short-lived rise. The findings indicate that 1) prior chronic constraint of ovarian function to a single ovary did not alter the overall time course of new follicle growth culminating in ovulation after luteectomy; 2) the contralateral ovary provided the principal negative feedback regulation of gonadotropin secretion for some time after luteectomy even though it may not have been the exclusive site of new follicle growth; 3) whereas the ability of the luteectomized ovary to regulate tonic gonadotropin secretion was temporarily impaired, its ability to support the customary temporal pattern of follicle growth after luteal ablation was not; 4) some (contralateral) ovarian factor other than estradiol or progesterone apparently made a major contribution to the regulation of FSH secretion after luteectomy; and 5) folliculogenesis culminating in ovulation from a single follicle and the negative feedback regulation of tonic gonadotropin secretion in some circumstances may occur concurrently but separately on opposite ovaries or may occur at different times within the same ovary.

Animals↗

PubMed1977

Regulation of phosphorylase-phosphatase from skeletal muscle by phosphorylation of a regulator protein.

The inhibitory effect of a heat-stable regulator protein from skeletal muscle on the activity of phosphorylase-phosphatase (EC 3.1.3.17) was studied. The regulator protein was shown to be both phosphorylated and dephosphorylated in vivo as well as in vitro. The incorporation of phosphate into the regulator protein increased, while dephosphorylation decreased the ability of the protein to inhibit phosphatase activity. Our results suggest that the reversible phosphorylation of the regulator protein plays an essential role in the regulation of phosphorylase-phosphatase activity.

Animals↗

PubMed1979

Implementation of regulations and promotion of standards for protective measures in the absence of statutory regulations.

Asbestos regulations in the UK and several other countries are described, and it is suggested that these could be used as a basis for similar regulations in other countries which do not yet have them. Those aspects of the UK regulations which make them particularly applicable to all occupational situations in which asbestos dust might be emitted are listed. As a result of such regulations, standards of control have improved; two examples are given.

Asbestos↗

PubMed2026

Antagonistic regulation by mango MiSPL9a and MiSPL9b regulates flowering time, drought and salt stress in Arabidopsis.

SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, which are unique to plants, contain a highly conserved SBP domain that regulates gene expression by binding to downstream targets. They play critical roles in various biological processes, especially in the regulation of flowering in plants. In this study, two SPL-like genes (MiSPL9a and MiSPL9b) were identified from mango genomic and transcriptomic data, and their sequence, expression and function were further analyzed. Sequence analysis revealed that MiSPL9a and MiSPL9b have open reading frames of 1173 bp and 1158 bp, respectively, with slight differences in the number of cis-regulatory elements within their promoter regions. Expression analysis under stress conditions revealed distinct patterns: MiSPL9a expression significantly differed under drought stress but did not significantly differ under salt stress, whereas MiSPL9b expression responded significantly to salt stress but changed minimally under drought stress. Phenotypic analysis of the transgenic Arabidopsis lines revealed that MiSPL9a overexpression delayed flowering, whereas MiSPL9b overexpression promoted early flowering. Under stress conditions, compared with wild-type plants, MiSPL9a-overexpressing plants presented increased drought tolerance but did not significantly differ. In contrast, MiSPL9b-overexpressing plants were sensitive to salt stress, with no notable phenotypic differences observed under drought conditions. Physiological assays revealed that under drought stress, MiSPL9a transgenic plants presented significantly reduced levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) and increased proline (Pro) content and superoxide dismutase (SOD) activity. Under salt stress, MiSPL9b transgenic plants presented opposite trends in terms of these physiological markers. In summary, both MiSPL9a and MiSPL9b are involved in the regulation of plant flowering time and stress responses, but their functions differ.

Arabidopsis↗

PubMed1979

[Substrate and parasubstrate regulation of physiological processes at various levels of the organization of living systems as illustrated by examples of the regulation of appetite, of the specific dynamic action of food and of the inhibition of processes of absorption].

It was demonstrated that in the organism of higher animals the adaptation regulation of food uptake and nutrient absorption and transport comprises, in addition to the classic mechanisms of substrate regulation, specialized non-substrate and parasubstrate mechanisms which control the uptake of food and other substrates at all three levels (organosystemic, organic and cellular). As to the organosystemic level, it was observed in duodenectomized rats that appetite inhibition is produced not only by a stimulation of the receptors and by an increase in the concentration of the food substrates and of the metabolites in the blood, but also by one of the intestinal appetite-inhibiting hormones, arenterin. As to the organic level, it was evidenced that the enzymatic and transport functions of the small intestine and the numerical composition of the enterocyte population in the different segments are determined by the substrate load on the respective areas of the small intestine as well as by the blood and chyme-mediated intersegmental reactions in the small intestine. As to the tissular and cellular levels, the possibility of a regulation of the enzymatic and transport systems of the microvilli by means of substrates contained in the mucous membrane of the small intestine and endogenous substances (permein and antipermein) was evinced.

Adaptation, Physiological↗

PubMed1978

Mechanisms of genetic resistance to Friend virus leukemia in mice. IV. Identification of a gene (Fv-3) regulating immunosuppression in vitro, and its distinction from Fv-2 and genes regulating marrow allograft reactivity.

Friend leukemia viru (FV) suppresses the proliferative response of normal lymphocytes to mitogens. The in vitro suppressive effect of FV on lymphocyte mitogenesis is mediated by T-suppressor cells and is under host genetic control. Lymphocytes from strains of mice of the C57BL background (e.g., C57BL/6) are resistant while cells from other strains (e.g., 129 and DBA/2) are susceptible. Genetic analyses utilizing resistant and susceptible parental strains, their F1, intercross and backcross progeny indicated that susceptibility to in vitro suppression is regulated by a single autosomal gene, dominant for susceptibility to suppression. This gene, which is not linked to the H-2 complex, segregated independently of the Fv-2 gene which controls resistance to spleen focus formation in vivo. The gene is also unlinked to the Ir-like genes which regulate the ability of H-2d mice to reject H-2b bone marrow grafts. The gene is therefore designated as Fv-3. Fv-3 may mediate its effect by regulating the numbers and/or functions of T-suppressor cells.

Animals↗

PubMed1976

[Mast cells as regulators of tissue homeostasis and their place in the series of biological regulators].

The most essential features of the mast cell are continuous production (and partially also absorption from the environment), deposition, and secretion of the two groups of biologically active substances of the regulatory type: heparin and other acid clycosaminoglycanes, and also histamine and, probably, other biogenic amines. These substances are antagonists and have an influence on the homeostasis of the microregion (capillary-connective tissue-parenchyma) -- the main area of action of the mast cells. The mast-cell population is characterized, as compared with other cellular populations of the microregion, by a smaller size, greater morphological and functional diversity, functional duality (capability of producing both a positive and negative effect), and therefore possesses a number of essential properties the biological regulator should meet. The system of mast cells differs from the regulators of a higher order (the nervous and endocrine system) by a smaller radius of action and a greater simplicity of the structure, the latter manifests itself in equality of all its components. The conclusion is drawn that mast cells may be considered as the regulators of tissue homeostasis and a last link in the general reaction of adaptation at the cellular level.

Anaphylaxis↗

PubMed1976

Regulation of rat adrenal dopamine beta-hydroxylase. II. Receptor interaction in the regulation of enzyme synthesis and degradation.

Rat adrenal gland dopamine beta-hydroxylase is under neuronal regulation from the splanchnic nerve and hormonal control via adrenal cortical glucocorticoids. The regulatory systems act in different ways; neuronal stimuli induce dopamine beta-hydroxylase synthesis while hormonal stimulation inhibits enzyme degradation. Despite these mechanistic differences, both systems require a normally innervated cholinergic receptor to exert their effect. The enzyme response to either neural stimulation or ACTH administration is blocked by splanchnic denervation. Glucocorticoid stimulation of dopamine beta-hydroxylase, however, can occur after adrenal denervation, suggesting that ACTH acts on a receptor which requires splanchnic innervation, but glucocorticoids act distal to the receptor. Similar results were obtained when the effect of these manipulations were studied on phenylethanolamine N-methyltransferase, another enzyme in the catecholamine biosynthetic pathway. A model attempting to unify these and earlier findings is presented, in which the splanchnic nerve is involved in regulating both adrenal cortical glucocorticoidogenesis (by allowing ACTH to act on glucocorticoid synthesis) and adrenal medullary catecholamine biosynthesis (by induction of enzyme synthesis.).

Adrenal Glands↗

PubMed1978

Regulation of protein synthesis in rabbit reticulocyte lysates by the heme-regulated protein kinase: inhibition of interaction of Met-tRNAfMet binding factor with another initiation factor in formation of Met-tRNAfMet.40S ribosomal subunit complexes.

Protein synthesis in reticulocytes and their lysates is regulated by heme. In heme deficiency a heme-regulated translational inhibitor (HRI) that blocks initiation of polypeptide chains is activated. HRI is a protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) that specifically phosphorylates the 38,000-dalton subunit of the Met-tRNA(f) (Met) binding factor (IF), which forms a ternary complex with Met-tRNA(f) (Met) and GTP, a finding that suggests that the inhibition by HRI involves the phosphorylation of IF. We have investigated the effect of HRI in the partial reactions of protein chain initiation in which the IF-promoted binding of Met-tRNA(f) (Met) to 40S ribosomal subunits is enhanced by another initiation factor [ternary complex dissociation factor (TDF)] and AUG. The results show that HRI at very low concentrations markedly inhibits the binding of Met-tRNA(f) (Met) to 40S subunits. The inhibitory effect of HRI requires ATP. Under these conditions HRI phosphorylates only the 38,000-dalton subunit of IF. The TDF preparations not only promote the binding of the ternary complex to 40S subunits but also promote the dissociation of the ternary complex in the presence of 5 mM Mg(2+) at 0 degrees . The preincubation of purified IF alone with low concentrations of HRI and ATP does not significantly affect its capacity to form the ternary complex; however, the TDF-promoted dissociation of the ternary complex is inhibited. The nonhydrolyzable analog adenosine 5'-[beta,gamma-imido]triphosphate does not substitute for ATP. These findings suggest that phosphorylation causes a conformational modification in IF, which results in inhibition of the interaction between the ternary complex and TDF that is required for the binding of the ternary complex to 40S subunits.

Adenosine Triphosphate↗

PubMed1979

The interactions between calcium-dependent regulator protein of cyclic nucleotide phosphodiesterase and microtubule proteins. II. Association of calcium-dependent regulator protein with tubulin dimer.

The Ca2+-dependent regulator protein (CDR) of cyclic nucleotide phosphodiesterase (PDE) was reported to be a Ca2+-dependent regulator of microtubule (MT) assembly in the preceding paper. In this paper, the binding of Ca2+-CDR complex to tubulin dimer was investigated in order to elucidate the Ca2+-dependent inhibitory action of CDR on MT assembly. Purified microtubular proteins (PMPs) isolated from porcine brain did not affect the ability of CDR to activate Ca2+-activatable PDE, and did not include any inhibitory protein of Ca2+-activatable PDE. The binding of CDR to the tubulin dimer was observed on Sephadex G-200 gel filtration and ammonium sulfate fractionation in a Ca2+-dependent manner. CDR did not bind to microtubule associated proteins. We now assume that Ca2+-dependent inhibition of MT assembly by CDR is due to the binding of CDR to tubulin dimer in a Ca2+-dependent manner.

Animals↗

PubMed1975

Multiple regulation of nucleoside catabolizing enzymes: regulation of the deo operon by the cytR and deoR gene products.

The protein and repressor nature of two regulatory gene products in E. coli has been demonstrated, employing mutants with either amber or thermosensitive mutations. The regulatory genes are the cytR and the deoR genes, both of which contribute to the regulation of the synthesis of nucleoside catabolizing enzymes. Enzyme levels in strains with concurrent mutations in both regulatory genes are considerably higher than the sum of the levels in strains with a cytR or a deoR mutation alone, indicating a certain co-operativity between the two repressor proteins. The glucose repression of enzyme levels observed in the double regulatory mutant is similar to that found in a cytR mutant, and much more pronounced than the glucose effect in a deoR mutant. A model of the promoter-operator region in the deo operon is proposed.

Cytidine Deaminase↗

PubMed1979

Cellular regulation of mammalian sarcoma virus expression: a gene regulation model for oncogenesis.

Investigations aimed at defining cellular functions required for expression of transformation by mammalian sarcoma viruses have led to the isolation of a class of revertants that contain biologically active feline sarcoma virus, yet possess in vitro and in vivo properties of normal cells. The block to expression of the transformed state in these cellular revertants was spontaneously reversible at low frequency. Moreover, infection with certain helper viruses reversed the block at very high efficiency. Helper virus complementation was shown not to be a direct effect of helper virus functions expressed in the initially infected revertant cell. Rather, the helper virus acted indirectly by rescuing sarcoma virus and allowing it to infect and transform another cell within the revertant population. Using biochemical and immunologic techniques, it was possible to demonstrate a specific and very marked reduction in transcriptional and translational products of the sarcoma viral genome in the revertant cells. Findings that the reversal of this block was associated with reacquisition of the transformed phenotype, together with other evidence, suggest that reversion results from cellular transcriptional regulation of the integrated sarcoma virus genome. Reversion in this virus transformation system provides a model for oncogenesis resulting from derepression of cellular genes that possess malignant potential.

Animals↗

PubMed2025

Identification of a PRDM1-regulated T cell network to regulate atherosclerotic plaque inflammation.

BACKGROUND: Inflammation is a key driver of atherosclerosis, yet the mechanisms sustaining inflammation in human plaques remain poorly understood. This study uses a network-based approach to identify immune gene programs involved in the transition from low- to high-risk (rupture-prone) human atherosclerotic plaques. METHODS: Expression data from human carotid artery plaques, both stable (low-risk, n = 16) and unstable (high-risk, n = 27), were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA). Bayesian network inference, operated on the eigengene values from the WGCNA, further extended the WGCNA analysis, and similarity to the signature of T cell subsets was validated in single-cell RNA sequencing data of human plaques, and a loss-of-function study in a mouse model of atherosclerosis. In silico drug repurposing was performed to identify potential therapeutic targets. RESULTS: Our analysis revealed a distinct gene module with a prominent T cell signature, particularly in unstable plaques. Key regulatory factors, RUNX3, IRF7 and in particular PRDM1, were significantly downregulated in plaque T cells from symptomatic versus asymptomatic patients, indicating a protective role. Additionally, as PRDM1 is downstream of IRF7, we opted for PRDM1 as a key target. T cell-specific Prdm1 deficiency in Western-type diet fed Ldlr knockout mice featured accelerated plaque progression. Finally, as PRDM1 targeting drugs are not yet available, we performed in silico drug repurposing, identifying EGFR inhibitors as promising therapeutic candidates. CONCLUSIONS: This study highlights a PRDM1-regulated T cell network that distinguishes high-risk from low-risk plaques and demonstrates the regulatory role of T cell PRDM1 in controlling atherosclerosis, positioning this pathway as a promising therapeutic target.

Plaque, Atherosclerotic↗

PubMed1979

The pineal and regulation of fibrosis: pinealectomy as a model of primary biliary cirrhosis: roles of melatonin and prostaglandins in fibrosis and regulation of T lymphocytes.

Pinealectomy leads to increased formation of fibrous tissue in the abdominal cavity, increased skin pigmentation and elevated cholesterol and alkaline phosphatase levels. It also leads to reduced formation and/or action of prostaglandin (PG) E1 and thromboxane (TX) A2. PGE1 plays an important role in enhancing function of T suppressor lymphocytes which control overactive antibody-producing B lymphocytes. In primary biliary cirrhosis there are increased skin pigmentation, hepatic fibrosis, elevated cholesterol and alkaline phosphatase levels, defective T lymphocytes and hyperactive B lymphocytes. Primary biliary cirrhosis may be a pineal deficiency disease. Serotonin is important in the pineal and the serotonin antagonist methysergide may cause retroperitoneal fibrosis by interfering with pineal function. There is a good deal of other evidence which suggests that melatonin PGE1 and TXA2 are important in the regulation of fibrosis in other situations such as "collagen" diseases, lithium-induced fibrosis and cardiomyopathies. This suggests that enhancement of formation of PGE1 and TXA2 may be of value in diseases associated with excess fibrosis and defective T suppressor cell function. PGE1 levels may be raised by zinc, penicillin, penicillamine and essential fatty acids. TXA2 levels may be raised by low dose colchicine. These new approaches to treatment may prove safer and more effective than existing ones. They may be of value in disorders such as cardiomyopathy, Hodgkin's disease and other lymphomas, multiple sclerosis, Crohn's disease, atopy and other diseases in which defective T cell function is suspected.

Animals↗