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rdf:type |
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lifeskim:mentions |
umls-concept:C0001455,
umls-concept:C0007586,
umls-concept:C0007634,
umls-concept:C0010453,
umls-concept:C0035820,
umls-concept:C0086418,
umls-concept:C0174680,
umls-concept:C0205390,
umls-concept:C0208355,
umls-concept:C0237477,
umls-concept:C0243192,
umls-concept:C0458827,
umls-concept:C0597357,
umls-concept:C1135918,
umls-concept:C1155878
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pubmed:issue |
5
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pubmed:dateCreated |
1999-11-24
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pubmed:abstractText |
Hyperplasia of airway smooth muscle (ASM) contributes to the airway hyperresponsiveness that characterizes asthma. We have investigated the relationship between cAMP-induced growth arrest of ASM cells and thrombin-stimulated, extracellular-regulated protein kinase (ERK) activity, cyclin D1, and the restriction protein retinoblastoma. The beta(2)-adrenergic receptor agonist albuterol (100 nM) inhibited DNA synthesis after incubation with ASM for periods as brief as 1 h when these coincided with the timing of the restriction point. Inhibition of thrombin-stimulated DNA synthesis by albuterol (1-100 nM), 8-bromo-cAMP (300 microM), or prostaglandin E(2) (1 microM) was accompanied by a reduction in cyclin D1 protein levels. The ERK kinase inhibitor PD98059 (3-30 microM) attenuated thrombin-stimulated ERK phosphorylation and activity and the increase in cyclin D1 protein levels, as did albuterol (1-100 nM) or 8-bromo-cAMP (300 microM). In contrast, neither albuterol (100 nM) nor PD98059 (30 microM) reduced cyclin D1 mRNA levels between 4 and 20 h after thrombin addition, which suggests that elevation of cAMP regulates cyclin D1 by a post transcriptional mechanism. The proteasome inhibitor MG132 (30 and 100 nM) and the calpain I inhibitor N-acetyl-Leu-Leu-leucinal (10 microM) attenuated the reduction in thrombin-stimulated cyclin D1 levels in ASM exposed to albuterol (100 nM), 8-bromo-cAMP (300 microM), or the phosphodiesterase inhibitor isobutylmethylxanthine (100 microM). Thus, the cAMP-induced arrest of ASM in the G(1) phase of the cell cycle is associated with a proteasomal degradation of cyclin D1 protein and a reduced protein retinoblastoma phosphorylation that prevents passage through the restriction point.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/8-Bromo Cyclic Adenosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-2 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Albuterol,
http://linkedlifedata.com/resource/pubmed/chemical/Calpain,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0026-895X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
56
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1079-86
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10531416-8-Bromo Cyclic Adenosine Monophosphate,
pubmed-meshheading:10531416-Adrenergic beta-2 Receptor Agonists,
pubmed-meshheading:10531416-Adrenergic beta-Agonists,
pubmed-meshheading:10531416-Albuterol,
pubmed-meshheading:10531416-Calpain,
pubmed-meshheading:10531416-Cells, Cultured,
pubmed-meshheading:10531416-Cyclin D1,
pubmed-meshheading:10531416-Cysteine Endopeptidases,
pubmed-meshheading:10531416-DNA,
pubmed-meshheading:10531416-Dinoprostone,
pubmed-meshheading:10531416-Flavonoids,
pubmed-meshheading:10531416-G1 Phase,
pubmed-meshheading:10531416-Gene Expression Regulation,
pubmed-meshheading:10531416-Humans,
pubmed-meshheading:10531416-Leupeptins,
pubmed-meshheading:10531416-MAP Kinase Kinase 1,
pubmed-meshheading:10531416-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:10531416-Mitogen-Activated Protein Kinases,
pubmed-meshheading:10531416-Multienzyme Complexes,
pubmed-meshheading:10531416-Muscle, Smooth,
pubmed-meshheading:10531416-Phosphorylation,
pubmed-meshheading:10531416-Proteasome Endopeptidase Complex,
pubmed-meshheading:10531416-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10531416-RNA, Messenger,
pubmed-meshheading:10531416-Retinoblastoma Protein,
pubmed-meshheading:10531416-S Phase,
pubmed-meshheading:10531416-Thrombin,
pubmed-meshheading:10531416-Time Factors
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pubmed:year |
1999
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pubmed:articleTitle |
Beta2-adrenergic receptor agonists and cAMP arrest human cultured airway smooth muscle cells in the G(1) phase of the cell cycle: role of proteasome degradation of cyclin D1.
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pubmed:affiliation |
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia. a.stewart@pharmacology.unimelb.edu.au
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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