Linked Life Data

8940395

Source:http://linkedlifedata.com/resource/pubmed/id/8940395

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-1-23
pubmed:abstractText
We have shown previously that treatment of 3T3-L1 preadipocytes with prostaglandin F2alpha (PGF2alpha) and fluprostenol, a prostanoid FP2 receptor (FP receptor) agonist, inhibited adipocyte differentiation. In this study, we demonstrate that the inhibition by PGF2alpha is controlled by concentrations of PGF2alpha rather than regulation of FP receptor levels or binding. Membranes prepared from either 3T3-L1 preadipocytes or adipocytes exhibited specific binding for PGF2alpha, suggesting that FP receptors are present throughout differentiation. Endogenous PGF2alpha production in 3T3-L1s was lower in differentiating cells compared with uninduced preadipocytes, providing further evidence that regulation occurs at the level of ligand concentration. Stimulation of the FP receptor causes a transient intracellular calcium increase, an activation of a calcium/calmodulin-dependent protein kinase (CaMK), and an increase in DNA synthesis, associated with the inhibition of differentiation. Calcium mobilizing agents, A23187 and thapsigargin, mimic the FP receptor-induced inhibition of differentiation, suggesting a role for calcium. KN-62, a CaMK inhibitor, reversed the inhibition of differentiation when added to differentiating cells with fluprostenol, suggesting a critical role for a CaMK in the inhibition. The activation of CaMK was responsible for an increase in DNA content and thymidine incorporation. The increase in DNA synthesis occurs without a concomitant increase in cell proliferation. Early differentiation markers remain intact with PGF2alpha treatment, defining the interference with normal postconfluent mitosis as the time period of differentiation that is affected by PGF2alpha. These results implicate the modulation of PGF2alpha levels in the inhibition of 3T3-L1 adipocyte differentiation through an FP receptor-mediated increase in intracellular calcium and associated increase in DNA synthesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
137
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5641-50
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
The mechanism of inhibition of 3T3-L1 preadipocyte differentiation by prostaglandin F2alpha.
pubmed:affiliation
Department of Biochemistry, The University of Wisconsin-Madison, 53706, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.