Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-2-20
pubmed:abstractText
Atrial natriuretic peptide (ANP) has been shown to inhibit the proliferation of various types of cells including glomerular mesangial cells. The activation of mitogen-activated protein kinase (MAPK) is one of the main signal transduction systems leading to cell proliferation. MAPK is tightly regulated by the activating kinase, MEK, and specific phosphatase MKP-1. Constitutive expression of MKP-1 has been shown to inhibit cell proliferation by suppressing MAPK activity. In order to understand the mechanism of the anti-proliferative effect of ANP, we examined whether ANP could inhibit MAPK by inducing MKP-1 in cultured rat glomerular mesangial cells. ANP increased the expression of MKP-1 mRNA in a dose-dependent (10 nM maximum) and time-dependent, with a peak stimulation at 30 min, manner. Receptor for ANP is a transmembrane guanylyl cyclase. Activation of guanylyl cyclase of ANP receptor by ligand plays an essential role in ANP signal transduction. 8-Bromo-cGMP, a cell permeable analogue of cyclic GMP, and sodium nitroprusside, an activator of soluble guanylyl cyclase, could mimic the effects of ANP and were able to induce the expression of MKP-1 in a similar time course as ANP. The protein expression of MKP-1 was maximally stimulated by ANP at 120 min. Treatment of the cells with ANP for 120 min resulted in an inhibition of phorbol ester-induced activation of MAPK, while the activation of MEK was not affected by ANP. These results indicate that ANP might inhibit the proliferation of mesangial cells by inactivating MAPK through the induction of MKP-1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
544-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8550616-Amino Acid Sequence, pubmed-meshheading:8550616-Animals, pubmed-meshheading:8550616-Atrial Natriuretic Factor, pubmed-meshheading:8550616-Cell Cycle Proteins, pubmed-meshheading:8550616-Cell Division, pubmed-meshheading:8550616-Cells, Cultured, pubmed-meshheading:8550616-Dual Specificity Phosphatase 1, pubmed-meshheading:8550616-Enzyme Activation, pubmed-meshheading:8550616-Gene Expression Regulation, Enzymologic, pubmed-meshheading:8550616-Glomerular Mesangium, pubmed-meshheading:8550616-Immediate-Early Proteins, pubmed-meshheading:8550616-Male, pubmed-meshheading:8550616-Molecular Sequence Data, pubmed-meshheading:8550616-Phosphoprotein Phosphatases, pubmed-meshheading:8550616-Protein Kinases, pubmed-meshheading:8550616-Protein Phosphatase 1, pubmed-meshheading:8550616-Protein Tyrosine Phosphatases, pubmed-meshheading:8550616-Rats, pubmed-meshheading:8550616-Rats, Sprague-Dawley
pubmed:year
1996
pubmed:articleTitle
Atrial natriuretic peptide induces the expression of MKP-1, a mitogen-activated protein kinase phosphatase, in glomerular mesangial cells.
pubmed:affiliation
Third Department of Medicine, Shiga University of Medical Science, Japan.
pubmed:publicationType
Journal Article