Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2000-2-29
pubmed:abstractText
We investigated the mechanisms of transforming growth factor-beta1 (TGF-beta1) inhibition on transforming growth factor-alpha (TGF-alpha)-induced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes. TGF-alpha (1.0 ng/ml) produced a 4.2-fold elevation of DNA synthesis during 3 h of culture and a 1. 2-fold increase in nucleus number (proliferation) during 4 h of culture. TGF-beta1 dose dependently inhibited the TGF-alpha-induced hepatocyte DNA synthesis and proliferation: half-maximal inhibition occurred at a TGF-beta1 concentration of 0.08 ng/ml. The inhibitory effects of 1.0 ng/ml TGF-beta1 were almost completely reversed by adenylate cyclase inhibitors, 2,4-dideoxyadenosine (10(-6) M), and somatostatin (3 x 10(-7) M), or by a specific inhibitor of protein kinase A, H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10(-7) M). In addition, while TGF-alpha did not affect the basal cellular adenosine 3',5'-monophosphate (cAMP) levels, TGF-beta1 was found to produce dose-dependent increases in cellular cAMP levels. The cAMP-elevating effects of TGF-beta1 were also reversed by 2,4-dideoxyadenosine (10(-6) M), and somatostatin (3 x 10(-7) M), but not by H-89 (10(-7) M). The present results suggest that the specific mechanisms involved in the growth inhibitory effect of TGF-beta1 on TGF-alpha-induced hepatocyte DNA synthesis and proliferation are via stimulation of adenylate cyclase, which increases intracellular cAMP and subsequently activates protein kinase A.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-2 Receptor Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-2 Receptor..., http://linkedlifedata.com/resource/pubmed/chemical/Antimetabolites, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/Dideoxyadenosine, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines, http://linkedlifedata.com/resource/pubmed/chemical/N-(2-(4-bromocinnamylamino)ethyl)-5-..., http://linkedlifedata.com/resource/pubmed/chemical/Somatostatin, http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
386
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
271-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:10618479-Adrenergic Agonists, pubmed-meshheading:10618479-Adrenergic Antagonists, pubmed-meshheading:10618479-Adrenergic beta-2 Receptor Agonists, pubmed-meshheading:10618479-Adrenergic beta-2 Receptor Antagonists, pubmed-meshheading:10618479-Animals, pubmed-meshheading:10618479-Antimetabolites, pubmed-meshheading:10618479-Cell Division, pubmed-meshheading:10618479-Cells, Cultured, pubmed-meshheading:10618479-Cyclic AMP, pubmed-meshheading:10618479-DNA, pubmed-meshheading:10618479-Dideoxyadenosine, pubmed-meshheading:10618479-Dose-Response Relationship, Drug, pubmed-meshheading:10618479-Drug Interactions, pubmed-meshheading:10618479-Enzyme Inhibitors, pubmed-meshheading:10618479-Isoquinolines, pubmed-meshheading:10618479-Liver, pubmed-meshheading:10618479-Male, pubmed-meshheading:10618479-Rats, pubmed-meshheading:10618479-Rats, Wistar, pubmed-meshheading:10618479-Somatostatin, pubmed-meshheading:10618479-Sulfonamides, pubmed-meshheading:10618479-Transforming Growth Factor alpha, pubmed-meshheading:10618479-Transforming Growth Factor beta
pubmed:year
1999
pubmed:articleTitle
Transforming growth factor-beta1 inhibits the growth of primary adult rat hepatocyte cultures by increasing cAMP levels.
pubmed:affiliation
Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Josai University, 1-1, Keyakidai, Sakado City, Japan.
pubmed:publicationType
Journal Article