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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic fate of labeled guanine and of prelabeled guanine nucleotides (GuRN) was studied in cultured rat cardiomyocytes. Special attention was given to guanine salvage in comparison to degradation; to the contribution of GuRN to adenine nucleotides (AdRN); to the fluxes from GMP to IMP and from IMP to GMP; and to the degradation pathways of GuRN. In accordance with the 3- to 4-fold higher activity of guanine deaminase (guanase), in comparison to that of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the rate of guanine deamination to xanthine exceeded that of guanine incorporation into nucleotides (at 4 microM) by 13.2-fold. The label from guanine incorporated into nucleotides was found mainly (81%) in GuRN, but also in IMP and AdRN. The prelabeled GuRN lost 43% of the label in 4 h, reflecting mainly degradation to xanthine (and uric acid) and synthesis of nucleic acids. Blocking nucleoside degradation was associated with a marked accumulation of label in guanosine and inosine (guanosine/inosine labeling ratio is 1.25). The results indicate that in the myocardium guanine is a poor substrate for salvage synthesis of GuRN and that its contribution to the homeostasis of adenine nucleotides is negligible; that GMP degradation to xanthine proceeds through both guanosine and IMP; and that the cardiomyocytes contain the activity of GMP reductase and of the enzymes converting IMP to GMP.
Biochem Mol Med 1995 Aug
PMID:Metabolism of guanine and guanine nucleotides in primary rat cardiomyocyte cultures. 758 72

Blocking K+ channels induces hormone secretion in various pituitary cell lines by a mechanism which is not completely delineated. In the present study, we employed the mouse pituitary tumor-derived AtT-20 cell as a model to evaluate this phenomenon. We correlated the effect of the K+ channel-blocker, tetraethylammonium (TEA), on K+ current and membrane potential utilizing whole cell recording, on cytosol Ca2+ ([Ca2+]i) concentration utilizing fura-2, and on ACTH secretion utilizing a perifusion system. TEA inhibited voltage-dependent K+ current and initiated membrane depolarization in a dose-dependent fashion. Divergences in the sensitivity to TEA between voltage-dependent K+ currents and membrane depolarization indicate that voltage-dependent K+ channels are not responsible for TEA-induced depolarization TEA (1-30 mM) also induced a concentration-dependent rise in [Ca2+]i concentration and ACTH secretion, both of which were inhibited by removing medium Ca2+. Our data indicate that TEA inhibits K+ currents and induces membrane depolarization; this opens Ca2+ channels in the plasmalemma, causing a rise in [Ca2+]i which initiates ACTH secretion. Alteration of K+ channel permeability by hormones or neurotransmitters may thus play an important regulatory role in controlling pituitary hormone secretion.
Mol Cell Endocrinol 1995 Mar
PMID:Blocking K+ channels with TEA induces plasmalemma depolarization, increased [Ca2+]i, and ACTH secretion in AtT-20 cells. 778 10

We used three interventions to test critically the theory that ischemic preconditioning is the result of translocation of cytosolic protein kinase C (PKC) into the membranes where it can be activated. If that theory were true then kinase activity should not be necessary during the preconditioning ischemia and thus blocking kinase activity at this time should not block protection. Secondly, since most translocation processes in the cell are accomplished by cytoskeletal microtubules, disrupting them with colchicine should also block protection from preconditioning. Finally, translocating PKC by transient exposure to PMA, should still require adenosine receptor activation to reactivate the PKC pathway during the subsequent ischemia. Blocking kinase activity with staurosporine during a 30 min insult completely blocks protection in preconditioned hearts but when staurosporine treatment was confined to the preconditioning episode protection was not blocked in five of the eight hearts studied. Microtubule disruption with colchincine did block the protective effect of preconditioning (38.3 +/- 1.9% infarction v 40.6 +/- 4.1% in non-preconditioned). Colchicine had no effect on infarct size in the non-preconditioned group. Five min PMA treatment plus 10 min washout significantly limited infarct size in isolated rabbit hearts subjected to 30 min regional ischemia (5.9 +/- 1.1% v 31 +/- 3.5% infarction in control). PMA's protection was blocked by adding the adenosine receptor blocker, SPT, during the sustained ischemia (38.1 +/- 6.1% infarction). All three of these experiments strongly support the translocation theory of ischemic preconditioning.
J Mol Cell Cardiol 1994 May
PMID:Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium. 807 20

Cell numbers are regulated by a balance among proliferation, growth arrest, and programmed cell death. A profound example of cell homeostasis, controlled throughout life, is the complex process of blood cell development, yet little is understood about the intracellular mechanisms that regulate blood cell growth arrest and programmed cell death. In this work, using transforming growth factor beta 1 (TGF beta 1)-treated M1 myeloid leukemia cells and genetically engineered M1 cell variants, the regulation of growth arrest and apoptosis was dissected. Blocking of early expression of MyD118, a novel differentiation primary response gene also shown to be a primary response gene induced by TGF beta 1, delayed TGF beta 1-induced apoptosis, demonstrating that MyD118 is a positive modulator of TGF beta 1-mediated cell death. Elevated expression of bcl-2 blocked the TGF beta 1-induced apoptotic pathway but not growth arrest induced by TGF beta 1. Deregulated expression of either c-myc or c-myb inhibited growth arrest and accelerated apoptosis, demonstrating for the first time that c-myb plays a role in regulating apoptosis. In all cases, the apoptotic response was correlated with the level of MyD118 expression. Taken together, these findings demonstrate that the primary response gene MyD118 and the c-myc, c-myb, and bcl-2 proto-oncogenes interact to modulate growth arrest and apoptosis of myeloid cells.
Mol Cell Biol 1994 Apr
PMID:The novel primary response gene MyD118 and the proto-oncogenes myb, myc, and bcl-2 modulate transforming growth factor beta 1-induced apoptosis of myeloid leukemia cells. 813 40

Polyamine-mediated degradation of vertebrate ornithine decarboxylase (ODC) is associated with the production of antizyme, a reversible tightly binding protein inhibitor of ODC activity. The interaction of antizyme with a binding element near the N terminus of ODC is essential but not sufficient for regulation of the enzyme by polyamines (X. Li and P. Coffino, Mol. Cell. Biol. 12:3556-2562, 1992). We now show that a second element present at the C terminus is required for the degradation process. Antizyme caused a conformational change in ODC, which made the C terminus of ODC more accessible. Blocking the C terminus with antibody prevented degradation. Tethering the C terminus by creating a circularly permuted, enzymatically active form of ODC prevented antizyme-mediated degradation. These data elucidate a form of feedback regulation whereby excess polyamines induce destruction of ODC, the enzyme that initiates their biosynthesis.
Mol Cell Biol 1993 Apr
PMID:Degradation of ornithine decarboxylase: exposure of the C-terminal target by a polyamine-inducible inhibitory protein. 845 17

In the current study, we have addressed the role of interferons (IFNs) in controlling the differentiation of pluripotent P19 embryonal carcinoma (EC) cells. Blocking IFN activity in the culture medium of differentiating cells with antibodies leads to a strong decrease in the degree of differentiation. The antibodies are active for a relatively short time. During this time, IFN-beta mRNA can be detected in the differentiating cells, as can increases of IFN stimulation response element-binding activity and NF-KB. The timing of IFN action also coincides with the accumulation of cytoplasmic double-stranded RNA (dsRNA) and with a drop in dsRNA unwindase-modificase activity. A model for the involvement of autoinduction of IFN by intracellular dsRNA in the control of differentiation in this system is presented.
Mol Cell Biol 1993 May
PMID:Action of spontaneously produced beta interferon in differentiation of embryonal carcinoma cells through an autoinduction mechanism. 847 45

Neu differentiation factor (NDF)-induced signaling involves the activation of members of the ErbB family of receptor tyrosine kinases. Although ectopic expression of recombinant ErbB receptors has yielded valuable insight into their signaling properties, the biological function and in vivo interplay of these receptors are still poorly understood. We addressed this issue by studying NDF signaling in various human cell lines expressing moderate levels of all known ErbB receptors. NDF-induced phosphorylation of ErbB-2 and ErbB-3 was found in the breast epithelial cell line MCF10A, the breast tumor cell lines T47D and MCF7, and the ovarian tumor cell line OVCAR3. Despite similar expression levels, NDF-induced phosphorylation of ErbB-4 was cell specific and only detected in T47D and OVCAR3 cells. Blocking cell surface expression of ErbB-2 by intracellular expression of a single-chain antibody revealed that in these two cell lines, ErbB-2 significantly enhanced phosphorylation of ErbB-4. Efficient NDF-induced phosphorylation of ErbB-3 was strictly ErbB-2 dependent in the breast tumor cell lines T47D and MCF7, while it was largely ErbB-2 independent in MCF10A and OVCAR3 cells. Consequently, NDF-stimulated intracellular signaling and induction of a biological response displayed a cell-specific requirement for ErbB-2. Thus, while ErbB-2 cooperates with NDF receptors in the breast tumor cell lines, ErbB-2 independent mechanisms seem to prevail in other cellular contexts.
Mol Cell Biol 1995 Dec
PMID:Neu differentiation factor activation of ErbB-3 and ErbB-4 is cell specific and displays a differential requirement for ErbB-2. 852 14

Blocking of L-type Ca channels by highly hydrophilic dihydropyridines, NKY-722 and KV-1360, was investigated in single ventricular cells of guinea-pig hearts using the whole-cell voltage clamp technique. At a holding potential of -30 mV, NKY-722 (1-100 nM) decreased the amplitude of the L-type Ca channel current (ICa) in a concentration-dependent manner. NKY-722 did not change the time constants of the decay of ICa. In the presence of NKY-722 (1 microM), the steady-state inactivation curve was shifted toward a more negative potential (by -33.0 +/- 2.0 mV) without changing its slope factor. The use-dependent block was elicited at a pulse frequency of 3.3 Hz or more. Even after washing out the drug at -80 mV for 20 min, ICa inhibited by NKY-722 (100 nM) at -30 mV was scarcely recovered when the membrane potential was clamped back to -30 mV. A permanently charged compound KV-1360 (0.1-1 microM), a quaternary amine derivative of NKY-722, hardly affected ICa by intracellular and extracellular application. These results suggest that, in spite of the high degree of ionization (91% in the charged form at pH 7.4), the mode of the L-type Ca channel block by NKY-722 is quite similar to that by lipophilic dihydropyridines. Consequently, the neutral form of NKY-722 is the active compound and this reaches the dihydropyridine receptor by "membranous approach".
J Mol Cell Cardiol 1995 Jun
PMID:L-type Ca channel block by highly hydrophilic dihydropyridines in single ventricular cells of guinea-pig hearts. 853 Dec 9

We examined possible roles of keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) in lung morphogenesis. By polymerase chain reaction, transcripts for both KGF and its receptor were detected early (rat gestational days 16 and 14, respectively) and their abundance increased during lung morphogenesis. To evaluate possible role of KGF in lung morphogenesis, day 14 lung explants were cultured in Dulbecco's modified Eagle medium + 10% fetal calf serum for 1 to 4 days in the presence (5-50 ng/ml) or absence of KGF (control). KGF (at 25 and 50 ng/ml) induced a marked reduction in the number of terminal branches and destination of the distal epithelium into cyst-like structures. These effects of exogenous KGF were progressively diminished by increasing concentrations of anti-KGF (2-16 micrograms/ml). Electron microscopic examination revealed that the epithelial cells of the cystic structures contained lamellar bodies, and were therefore type II cells and/or their progenitors. Northern blot analysis showed higher expression of surfactant protein C (SP-C) mRNA (a marker for alveolar epithelial type II cells) in KGF-treated fetal lungs. In situ hybridization of the KGF-treated lungs revealed that the SP-C mRNA-expressing cells were arranged distally in the form of linear arrays, a pattern distinctly different from that in control lungs. Acidic fibroblast growth factor, which also binds KGF receptors, in the presence of heparin mimicked the effect of KGF on branching. Transforming growth factor-beta(1) (TGF-beta 1) inhibited branching of fetal lungs in culture, and this effect dominated over that induced by KGF. Blocking of endogenous HGF with antibodies or addition of HGF to cultures of fetal lung explants had no significant effect on branching or growth. In conclusion, KGF markedly influences branching, and epithelial growth, differentiation, and patterning during lung morphogenesis.
Am J Respir Cell Mol Biol 1996 Sep
PMID:Keratinocyte growth factor and embryonic rat lung morphogenesis. 881 Jun 36

An important relationship between transcription and initiation of DNA replication in both eukaryotes and prokaryotes has been suggested. In an attempt to understand the molecular mechanism of this interaction, we examined whether transcription can induce DNA replication in vitro by constructing a system in which both replication and transcription were combined. Relaxed circular DNA possessing a replication initiation zone located upstream of the human c-myc gene and a T7 promoter near the P1 promoter of the gene was replicated in the presence of T7 RNA polymerase. In our model system, replication was carried out with the proteins required for simian virus 40 DNA replication. DNA synthesis, which was dependent on both T7 RNA polymerase and the replication proteins, was detected mainly in the promoter and upstream regions of the c-myc gene. Blocking RNA synthesis at the initial stage of the reaction severely reduced DNA synthesis, suggesting that RNA chain elongation is required to induce DNA synthesis. The results indicated that transcription can induce DNA replication in the upstream region of the transcribed gene, most likely by introducing negative supercoiling into the region, which results in unwinding of the DNA duplex.
Mol Cell Biol 1996 Oct
PMID:Induction of DNA replication by transcription in the region upstream of the human c-myc gene in a model replication system. 881 89


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