Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of our studies was to examine if the baroreceptor reflex induced by intravenous injection of nitroglycerin (NG) nearly nullifies the vasodilator action of NG on the systemic capacitance vessels in dogs anesthetized with pentobarbital. We performed total spinal anesthesia (TSA) in open-chest dogs to eliminate the baroreceptor reflex. Dogs in which mean blood pressure (MBP) was maintained at about 100 mmHg by continuous intravenous infusion of epinephrine formed the TSA 100 group, and those in which MBP was maintained at about 70 mmHg formed the TSA 70 group. Dose-response curves relating 5-6 different doses (0.8 to 200 micrograms/kg) of intravenous NG, to changes in mean circulatory pressure (% delta MCP) and to changes in total peripheral resistance (% delta TPR), were constructed. These data were compared with those from untreated dogs. In addition, we also studied plasma catecholamine (CA) concentrations before and after the intravenous injection of NG. (1) There was no significant difference in the dose-response curves of NG for % delta TPR between the 3 groups. (2) There was no significant difference in the dose-response curves for % delta MCP between the 2 TSA groups. However, there was significant difference in the dose-response curves for % delta MCP between the TSA groups and the untreated dogs. The dose-response curves for % delta MCP in the TSA groups shifted upwards as compared with that of the untreated dogs. (3) In the TSA 100 group, there was no significant increase in the plasma CA concentrations with 100 micrograms/kg of NG. In the untreated group, intravenous injection of 12.5 micrograms/kg and 100 micrograms/kg of NG caused a dose-related fall in MBP and a dose-related rise in the plasma norepinephrine and epinephrine concentrations. Our results suggest that the vasodilator action of NG on the systemic capacitance vessels in the untreated dogs was counterbalanced partly by the vasoconstriction produced by the baroreceptor reflex, with its direct vasodilator effect masked when the hypotensive doses of NG were given acutely.
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PMID:Differential vasodilator effect of nitroglycerin on systemic capacitance and resistance vessels in anesthetized dogs, and the mechanism of its action--a study by measuring mean circulatory pressure and total peripheral resistance. 251 38

The potentially deleterious effects of aberrant mRNA lacking a termination codon (nonstop mRNA) are ameliorated by translation arrest, proteasome-mediated protein destabilization, and rapid mRNA degradation. Because polylysine synthesis via translation of the poly(A) mRNA tail leads to translation arrest and protein degradation by the proteasome, we examined the effects of other amino acid sequences. Insertion of 12 consecutive basic amino acids between GFP and HIS3 reporter genes, but not a stem-loop structure, resulted in degradation of the truncated green fluorescent protein (GFP) products by the proteasome. Translation arrest products derived from GFP-R12-FLAG-HIS3 or GFP-K12-FLAG-HIS3 mRNA were detected in a not4Delta mutant, and MG132 treatment did not affect the levels of the truncated arrest products. Deletion of other components of the Ccr4-Not complex did not increase the levels of the translation arrest products or reporter mRNAs. A L35A substitution in the Not4p RING finger domain, which disrupted its interaction with the Ubc4/Ubc5 E2 enzyme and its activity as an ubiquitin-protein ligase, also abrogated the degradation of arrest products. These results suggest that Not4p, a component of the Ccr4-Not complex, may act as an E3 ubiquitin-protein ligase for translation arrest products. The results let us propose that the interaction between basic amino acid residues and the negatively charged exit tunnel of the ribosome leads to translation arrest followed by Not4p-mediated ubiquitination and protein degradation by the proteasome.
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PMID:Nascent peptide-dependent translation arrest leads to Not4p-mediated protein degradation by the proteasome. 1920 1