Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-2-9
pubmed:abstractText
In chronic liver injury, hepatic stellate cells (HSCs) have been implicated as regulators of sinusoidal vascular tone. We studied the relative role of Ca(2+)-dependent and Ca(2+)-independent contraction pathways in rat HSCs and correlated these findings to in situ perfused cirrhotic rat livers. Contraction of primary rat HSCs was studied by a stress-relaxed collagen lattice model. Dose-response curves to the Ca(2+) ionophore A-23187 and to the calmodulin/myosin light chain kinase inhibitor W-7 served to study Ca(2+)-dependent pathways. Y-27632, staurosporin, and calyculin (inhibitors of Rho kinase, protein kinase C, and myosin light chain phosphatase, respectively) were used to investigate Ca(2+)-independent pathways. The actomyosin interaction, the common end target, was inhibited by 2,3-butanedione monoxime. Additionally, the effects of W-7, Y-27632, and staurosporin on intrahepatic vascular resistance were evaluated by in situ perfusion of normal and thioacetamide-treated cirrhotic rat livers stimulated with methoxamine (n = 25 each). In vitro, HSC contraction was shown to be actomyosin based with a regulating role for both Ca(2+)-dependent and -independent pathways. Although the former seem important, an important auxiliary role for the latter was illustrated through their involvement in the phenomenon of "Ca(2+) sensitization." In vivo, preincubation of cirrhotic livers with Y-27632 (10(-4) M) and staurosporin (25 nM), more than with W-7 (10(-4) M), significantly reduced the hyperresponsiveness to methoxamine (10(-4) M) by -66.8 +/- 1.3%, -52.4 +/- 2.7%, and -28.7 +/- 2.8%, respectively, whereas in normal livers this was significantly less: -43.1 +/- 4.2%, -40.2 +/- 4.2%, and -3.8 +/- 6.3%, respectively. Taken together, these results suggest that HSC contraction is based on both Ca(2+)-dependent and -independent pathways, which were shown to be upregulated in the perfused cirrhotic liver, with a predominance of Ca(2+)-independent pathways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Actomyosin, http://linkedlifedata.com/resource/pubmed/chemical/Amides, http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Diacetyl, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Methoxamine, http://linkedlifedata.com/resource/pubmed/chemical/Myosin-Light-Chain Kinase, http://linkedlifedata.com/resource/pubmed/chemical/Oxazoles, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Pyridines, http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine, http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides, http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents, http://linkedlifedata.com/resource/pubmed/chemical/W 7, http://linkedlifedata.com/resource/pubmed/chemical/Y 27632, http://linkedlifedata.com/resource/pubmed/chemical/calyculin A, http://linkedlifedata.com/resource/pubmed/chemical/diacetylmonoxime
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
292
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G556-64
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17008556-Actomyosin, pubmed-meshheading:17008556-Amides, pubmed-meshheading:17008556-Animals, pubmed-meshheading:17008556-Calcimycin, pubmed-meshheading:17008556-Calcium, pubmed-meshheading:17008556-Cell Shape, pubmed-meshheading:17008556-Cells, Cultured, pubmed-meshheading:17008556-Diacetyl, pubmed-meshheading:17008556-Enzyme Inhibitors, pubmed-meshheading:17008556-Liver, pubmed-meshheading:17008556-Male, pubmed-meshheading:17008556-Methoxamine, pubmed-meshheading:17008556-Myocytes, Cardiac, pubmed-meshheading:17008556-Myocytes, Smooth Muscle, pubmed-meshheading:17008556-Myosin-Light-Chain Kinase, pubmed-meshheading:17008556-Oxazoles, pubmed-meshheading:17008556-Protein Kinase Inhibitors, pubmed-meshheading:17008556-Pyridines, pubmed-meshheading:17008556-Rats, pubmed-meshheading:17008556-Rats, Wistar, pubmed-meshheading:17008556-Signal Transduction, pubmed-meshheading:17008556-Staurosporine, pubmed-meshheading:17008556-Sulfonamides, pubmed-meshheading:17008556-Vasoconstrictor Agents
pubmed:year
2007
pubmed:articleTitle
Both Ca2+ -dependent and -independent pathways are involved in rat hepatic stellate cell contraction and intrahepatic hyperresponsiveness to methoxamine.
pubmed:affiliation
Dept of Hepatology, Univ Hospital Gasthuisberg, K U Leuven, Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't