rdf:type |
|
lifeskim:mentions |
umls-concept:C0001675,
umls-concept:C0010453,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0062534,
umls-concept:C0205225,
umls-concept:C0227525,
umls-concept:C0752312,
umls-concept:C1879547,
umls-concept:C1948023,
umls-concept:C2917450
|
pubmed:issue |
4
|
pubmed:dateCreated |
2007-4-19
|
pubmed:abstractText |
We investigated the effects of alpha(1)- and beta(2)-adrenergic agonists on hepatocyte growth factor (HGF)-stimulated mitogen-activated protein kinase (MAPK) isoforms in primary cultures of adult rat hepatocytes. Hepatocytes were isolated and cultured with HGF (5 ng/ml) and/or alpha- and beta-adrenergic agonists. Phosphorylated MAPK isoforms (p42 and p44 MAPK) were detected by Western blotting analysis using anti-phospho-MAPK antibody. The results show that HGF increased phosphorylation of p42 MAPK by 2.2-fold within 3 min. The HGF-induced MAPK activation was abolished by AG1478 treatment (10(-7) M). The MEK (MAPK kinase) inhibitor PD98059 (10(-6) M) completely inhibited the HGF-dependent increase in MAPK activity. Phenylephrine (10(-6) M) and metaproterenol (10(-6) M) alone had no effect in the absence of HGF, but significantly increased p42 MAPK induction by HGF. Moreover, the cell-permeable cAMP analog, 8-bromo cAMP (10(-7) M), and phorbol 12-myristate 13 acetate (10(-7) M) potentiated HGF-induced MAPK phosphorylation. The effects of these analogs were antagonized by the protein kinase A (PKA) inhibitor H-89 (10(-7) M) and the protein kinase C (PKC) inhibitor sphingosine (10(-6) M), respectively. These results suggest that direct or indirect activation of both PKA and PKC represent a positive regulatory mechanism for stimulating MAPK induction by HGF.
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/8-Bromo Cyclic Adenosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-1 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-2 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Androstadienes,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, 70-kDa,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin AG 1478,
http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
|
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
1347-8613
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:volume |
103
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
398-407
|
pubmed:dateRevised |
2010-11-18
|
pubmed:meshHeading |
pubmed-meshheading:17409628-8-Bromo Cyclic Adenosine Monophosphate,
pubmed-meshheading:17409628-Adrenergic Agonists,
pubmed-meshheading:17409628-Adrenergic alpha-1 Receptor Agonists,
pubmed-meshheading:17409628-Adrenergic beta-2 Receptor Agonists,
pubmed-meshheading:17409628-Androstadienes,
pubmed-meshheading:17409628-Animals,
pubmed-meshheading:17409628-Cells, Cultured,
pubmed-meshheading:17409628-Dose-Response Relationship, Drug,
pubmed-meshheading:17409628-Enzyme Activation,
pubmed-meshheading:17409628-Enzyme Inhibitors,
pubmed-meshheading:17409628-Flavonoids,
pubmed-meshheading:17409628-Hepatocyte Growth Factor,
pubmed-meshheading:17409628-Hepatocytes,
pubmed-meshheading:17409628-Male,
pubmed-meshheading:17409628-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:17409628-Mitogen-Activated Protein Kinases,
pubmed-meshheading:17409628-Models, Biological,
pubmed-meshheading:17409628-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17409628-Phosphorylation,
pubmed-meshheading:17409628-Rats,
pubmed-meshheading:17409628-Rats, Wistar,
pubmed-meshheading:17409628-Ribosomal Protein S6 Kinases, 70-kDa,
pubmed-meshheading:17409628-Sirolimus,
pubmed-meshheading:17409628-Sphingosine,
pubmed-meshheading:17409628-Tyrphostins
|
pubmed:year |
2007
|
pubmed:articleTitle |
Activation of mitogen-activated protein kinase by hepatocyte growth factor is stimulated by both alpha1- and beta2-adrenergic agonists in primary cultures of adult rat hepatocytes.
|
pubmed:affiliation |
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai, Sakado, Saitama, Japan. mkimura@josai.ac.jp
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|