Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1995-5-3
pubmed:abstractText
Endothelin-1 (ET-1) stimulates vascular smooth muscle and mesangial cells to release prostaglandin E2 (PGE2), which can attenuate the vasoconstrictor and mitogenic effects of this peptide. Phospholipase A2 (PLA2)-mediated release of arachidonic acid from the sn-2 position of membrane phospholipids is thought to be one of the rate-limiting steps in prostaglandin (PG) synthesis. We evaluated the role of ET-1 to regulate gene expression, protein synthesis and enzymatic activity of cytosolic PLA2 (cPLA2), an intracellular form of the PLA2 enzyme family, in cultured rat mesangial cells using both acute and chronic incubation protocols. Acute ET-1-induced stimulation of cPLA2 activity was maximal after 10 minutes (181.1 +/- 6.84% of control), persisted for 40 minutes and did not require new protein synthesis. Heparin, a potent inhibitor of intracellular Ca2+ increase as well as mitogen-activated protein (MAP) kinase activation and cell proliferation, did not affect the rapid cPLA2 stimulation by ET-1. Chronic incubation of glomerular mesangial cells with ET-1 (1 to 24 hr) led to time- and dose-dependent increases in cPLA2 mRNA expression which was maximal after six hours, persisted up to 24 hours and which was accompanied by both cPLA2 protein formation, as assessed by Western analysis, as well as by stimulation of enzymatic activity. Inhibition of protein synthesis by cycloheximide increased basal cPLA2 mRNA accumulation in quiescent mesangial cells, and the combination of ET-1 and cycloheximide resulted in a greater induction of cPLA2 gene expression when compared to ET-1 alone. Actinomycin D treatment blocked the effect of ET-1 on cPLA2 mRNA accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones, http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide, http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin, http://linkedlifedata.com/resource/pubmed/chemical/Endothelins, http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A, http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Quinones, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/herbimycin
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0085-2538
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1644-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Endothelin-1 stimulates cytosolic phospholipase A2 activity and gene expression in rat glomerular mesangial cells.
pubmed:affiliation
Department of Medicine, Case Western Reserve University, Cleveland, Ohio.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't