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

Isolated pituitary cells prepared from adrenalectomized rats secrete ACTH in response to CRF, and this response is inhibited by corticosterone. Both the stimulation of release by CRF and the inhibition of release by corticosterone are antagonized by cordycepin (3'-deoxyadenosine). Inhibition of CRF-stimulated secretion by cordycepin is apparently not related to inhibition of RNA synthesis, since high doses of actinomycin D do not affect ACTH secretion. More likely, cordycepin's inhibition of secretion stems from its inhibition of adenylate cyclase activity. Inhibition of corticosterone action by cordycepin is qualitatively similar to that previously reported actinomycin D. This effect of both drugs is probably due to inhibition of RNA synthesis. Significantly, a low dose of cordycepin has a greater inhibitory effect on corticosterone action than on total cellular RNA synthesis. Cordycepin is reported to preferentially inhibit messenger RNA synthesis, and low dose preferentially inhibits appearance of cytoplasmic RNA in pituitary cells. These data suggest that corticosterone-induced RNA is a cytoplasmic (messenger) RNA.
Mol Cell Endocrinol 1978 Jan
PMID:Effect of cordycepin on CRF stimulation and steroid inhibition of ACTH secretion by rat pituitary cells. 20 1

Adenosylcobalamin-dependent rearrangements are enzyme catalyzed reactions in which a hydrogen atom is transfered from one carbon atom to an adjacent one in exchange for a group X which migrates in the opposite direction. In the hydrogen transfer step, the mechanism of which is reasonably well understood, the cofactor serves as an intermediate hydrogen carrier. The transfer of hydrogen to the cofactor involves homolysis of the carbon-cobalt bond to generate cob(II) alamin and the 5'-deoxyadenos-5'-yl radical, followed by abstraction of a hydrogen atom from the substrate to form 5'-deoxyadenosine and the substrate radical. After migration of group X, the hydrogen atom is returned to the product radical by the reverse of the above reactions to generate the final product and reconstitute the cofactor. In contrast to the transfer of hydrogen, the mechanism of group X migration is poorly understood. Many reactions mechanisms have been proposed on chemical grounds, but there is insufficient biochemical evidence to permit a choice among these propsals. A quantity of negative evidence has accumulated suggesting that group X migration does not involve alkylation of the cobalt of cobalamin by the substrate, but in the absence of firm data supporting an alternative mechanism, even this weak conclusion must be regarded as provisional.
Mol Cell Biochem 1977 Apr 12
PMID:The mechanism of cobalamin-dependent rearrangements. 30 95

The selection at 22 degrees C of yeast cordycepin (3'-deoxyadenosine) sensitive mutants which would be temperature-sensitive at 37 degrees C allowed the obtention of mutants specifically impaired in processing of Poly(A)-containing RNAs at 37 degrees C. The mutants displaying this phenotype belong to two different loci. The biochemical study of the physiological function which is blocked by the mutation has revealed that the level of radioactive Poly(A)-containing RNAs found in a 5 min pulse after a 10 min shift at 37 degrees C is 6 times less in the mutants than in the wild type without reduction of the non Poly(A)-containing RNAs fraction. Further studies have shown no alteration in the two Poly(A) polymerases activities and suggest strongly a faster decay of Poly(A)-containing RNAs in the mutants.
Mol Gen Genet 1978 Oct 04
PMID:Yeast temperature-sensitive mutants specifically impaired in processing of poly(A)-containing RNAs. 36 72

The highly unstable c-myc mRNA has been shown to be stabilized in cells treated with protein synthesis inhibitors. We have studied this phenomenon in an effort to gain more insight into the degradation pathway of this mRNA. Our results indicate that the stabilization of c-myc mRNA in the absence of translation can be fully explained by the inhibition of translation-dependent poly(A) tail shortening. This view is based on the following observations. First, the normally rapid shortening of the c-myc poly(A) tail was slowed down by a translation block. Second, c-myc messengers which carry a short poly(A) tail, as a result of prolonged actinomycin D or 3'-deoxyadenosine treatment, were not stabilized by the inhibition of translation. We propose that c-myc mRNA degradation proceeds in at least two steps. The first step is the shortening of long poly(A) tails. This step requires ongoing translation and thus is responsible for the delay in mRNA degradation observed in the presence of protein synthesis inhibitors. The second step involves rapid degradation of the body of the mRNA, possibly preceded by the removal of the short remainder of the poly(A) tail. This last step is independent of translation.
Mol Cell Biol 1990 Dec
PMID:Poly(A) tail shortening is the translation-dependent step in c-myc mRNA degradation. 170 Oct 14

A primary culture of cells derived from uninvolved and atherosclerotic intima of human aorta was used to elucidate the role of cyclic nucleotides in atherogenesis. The cells cultured from fatty streaks and atherosclerotic plaques had a 2- to 8-fold lower cyclic AMP level and a 1.5- to 2-fold higher level of cyclic GMP compared with those of a grossly normal intima. Medial cells cultured from nonlesioned and atherosclerotic aortic segments showed no differences in the cyclic nucleotide concentrations. Reduction of the intracellular cyclic AMP with 2'-deoxyadenosine or a cyclic GMP elevation with its dibutyryl derivative, or liposomes containing cyclic GMP stimulated the uptake of [3H]thymidine and protein synthesis in the cells cultured from unaffected intima. On the contrary, a rise of the intracellular cyclic AMP caused by adenylate cyclase activators, a phosphodiesterase inhibitor, dibutyryl cyclic AMP, and liposomes containing cyclic AMP inhibited cell proliferation and protein synthesis. Elevation of the intracellular cyclic AMP stimulated the hydrolysis of lipids which led to reduction of lipid levels in the cells cultured from atherosclerotic lesions. The results of this study corroborate the existence of a relationship between the alterations of intracellular cyclic nucleotide levels and the metabolic disorders occurring in atherosclerosis.
Exp Mol Pathol 1987 Dec
PMID:Cyclic nucleotides and atherosclerosis: studies in primary culture of human aortic cells. 244

Transmembrane equilibration of 2',3'-dideoxyadenosine (ddAdo) was measured by rapid kinetic techniques in deoxycoformycintreated P388 and L1210 mouse leukemia cells and human erythrocytes, at 25 degrees. It was only about 10% as rapid as that of other purine nucleosides that are known substrates for the nucleoside transporters of these cells. ddAdo entry was nonsaturable up to a concentration of 1 mM and was not inhibited by other nucleosides or two nucleoside transport inhibitors, dipyridamole and nitrobenzylthioinosine. Thus, ddAdo permeation was mainly nonmediated. It was relatively rapid because of the high lipid solubility of ddAdo. ddAdo entered the cells at least 100 times more rapidly than dideoxycytidine but less rapidly than trideoxythymidine, with an even greater lipophilicity than ddAdo. ddAdo was not phosphorylated in human erythrocytes, but there was some phosphorylation in deoxycoformycin-treated P388 and L1210 cells. In situ conversion of 10 microM ddAdo to ddATP, however, was slow and ceased after 5-10 min at 25 degrees or 37 degrees. Cessation of net uptake was not due to turnover of dideoxy-ATP or deamination of dideoxy-AMP. The results suggest that ddAdo salvage in the absence of deamination is limited by feedback inhibition of its phosphorylation, perhaps by deoxycytidine kinase. Permeation into the cells was not rate limiting to ddAdo salvage. In P388 and L1210 cells that had not been treated with deoxycoformycin, ddAdo was salvaged at least 100 times more efficiently than in deoxycoformycin-treated cells and converted to nucleoside triphosphates, but the end-products and pathways of salvage have not been resolved entirely. Salvage of ddAdo required deamination but was not primarily via dideoxyinosine----hypoxanthine----IMP, as is the case for 2'-deoxyadenosine salvage, because [3H]ddAdo salvage was only little inhibited by unlabeled hypoxanthine, whereas it was strongly inhibited by 2'-deoxyadenosine, adenosine, and adenine.
Mol Pharmacol 1989 Jul
PMID:Permeation and salvage of dideoxyadenosine in mammalian cells. 278 72

Formation of mRNA 3' termini involves cleavage of an mRNA precursor and polyadenylation of the newly formed end. Cleavage of simian virus 40 late pre-mRNA in a crude nuclear extract generated two RNAs, 5' and 3' half-molecules. These RNAs were unmodified and linear. The 5' half-molecule contained sequences upstream but not downstream of the poly(A) site and ended in a 3'-terminal hydroxyl. The 3' half-molecules comprised a family of RNAs, each of which contains only sequences downstream of the poly(A) site, and ends in a 5'-terminal phosphate. These RNAs differed only in the locations of their 5' terminus. The 3' terminus of the 5' half-molecule was the adenosine 10 nucleotides downstream of AAUAAA, at the +1 position. The 5' terminus of the longest 3' half-molecule was at +2. Thus, these two RNAs contain every nucleoside and phosphate of the precursor. The existence of these half-molecules demonstrates that endonucleolytic cleavage occurs near the poly(A) site. 5' half-molecules generated in the presence of EDTA (which blocks polyadenylation, but not cleavage) ended at the adenosine at position +1 of the precursor. When incubated in the extract under suitable conditions, they became polyadenylated. 5' half-molecules formed in 3'-dATP-containing reactions contained a single 3'-deoxyadenosine (cordycepin) residue added onto the +1 adenosine and were poor polyadenylation substrates. We infer that the +1 adenosine of the precursor becomes the first A of the poly(A) tract and provides a 3' hydroxyl group to which poly(A) is added posttranscriptionally.
Mol Cell Biol 1987 Apr
PMID:Products of in vitro cleavage and polyadenylation of simian virus 40 late pre-mRNAs. 303 25

The separation by chromatofocusing of two distinct purine nucleoside cleaving activities from crude extracts of Trypanosoma brucei brucei is described. One catalyzes the reversible phosphorolysis of 5'-deoxy-5'-methylthioadenosine (MeSAdo) and adenosine (Ado) and was designated an MeSAdo/Ado phosphorylase, while the other catalyzes the hydrolysis of adenosine, inosine, and guanosine but not MeSAdo. The substrate specificity of trypanosomal MeSAdo/Ado phosphorylase differed from that of a mammalian MeSAdo phosphorylase (derived from murine Sarcoma 180 cells) in that it was able to phosphorolyze 2'-deoxyadenosine, 3'-deoxyadenosine and 2',3'-dideoxyadenosine. In addition, the trypanosomal phosphorylase was able to utilize the nucleoside analog, 6-methylpurine 2'-deoxyribonucleoside, as an alternative substrate, whereas the mammalian enzyme could not. Because of these differences, cytotoxic analogs of MeSAdo may be designed that are selectively activated by the trypanosomal MeSAdo/Ado phosphorylase.
Mol Biochem Parasitol 1988 Jan 15
PMID:Substrate specificities of 5'-deoxy-5'-methylthioadenosine phosphorylase from Trypanosoma brucei brucei and mammalian cells. 312 30

The activated dimonophosphate of 3'-deoxyadenosine (cordycepin) undergoes oligomerization to produce a new family of pyrophosphate-linked oligomers in which the average repeating unit involves a nine-atom structural group. The presence of a poly(U) template increases the relative yields of higher oligomers, although the template-free reaction is itself extremely efficient.
J Mol Evol 1987
PMID:Nucleic acid-like structures. III. Oligomerization of 3'-deoxyadenosine 2',5'-diphosphoimidazolide. 313 30

An adenosine-sensitive adenylate cyclase has been demonstrated in rat posterior pituitary in the present studies. N-Ethylcarboxamide adenosine (NECA), 2-chloroadenosine (2-Cl-Ado) and L-N6-phenylisopropyladenosine (PIA) all stimulated adenylate cyclase in a concentration-dependent manner, with an apparent Ka between 0.5 and 1 microM. NECA was most effective and stimulated adenylate cyclase by about 100%, whereas 2-Cl-Ado and PIA stimulated the enzyme activity by about 60%. The activation of adenylate cyclase by NECA was dependent on the concentrations of metal ions such as Mg2+ or Mn2+. The stimulatory effect of NECA on adenylate cyclase was completely blocked by 3-isobutyl-1-methylxanthine (IBMX) and 8-phenyltheophylline. Adenosine showed a biphasic effect on adenylate cyclase: stimulation at lower concentrations and inhibition at higher concentrations, whereas 2'-deoxyadenosine and 2'5'-dideoxyadenosine inhibited adenylate cyclase in a concentration-dependent manner. In addition, dopamine, isoproterenol and forskolin also stimulated adenylate cyclase to various degrees and the stimulatory effect of isoproterenol and forskolin was found to be additive with the stimulation exerted by NECA. These data indicate the presence of adenosine stimulatory receptors Ra/A2 in posterior pituitary which are coupled to adenylate cyclase. It is possible that adenosine may act as one of the important regulators to regulate and/or modulate the release of posterior pituitary hormones.
Mol Cell Endocrinol 1988 Jun
PMID:Adenosine interaction with adenylate cyclase in rat posterior pituitary. 340 62


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