Document Detail


Regulation of extracellular matrix remodeling and MMP-2 activation in cultured rat adrenal medullary endothelial cells.
MedLine Citation:
PMID:  11824476     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported that short-term exposure of cultured rat adrenal medullary endothelial cells (RAMEC) to thrombin enhances the subendothelial deposition of extracellular matrix (ECM) proteins fibronectin, laminin, and collagen types I (C-I) and IV (C-IV) (Papadimitriou et al. 1997). In this work, we extended our previous studies on factors that effect ECM protein deposition to include agents that activate or inhibit some of the most common intracellular signals such as cAMP, protein kinase C (PKC), and calcium. Furthermore, we investigated the possible link between the observed alterations in ECM protein deposition and the secretion of matrix metalloproteinase-2 (MMP-2). Forskolin (adenylyl cyclase activator) caused a dose-dependent increase in the deposition of all four ECM proteins studied. Isoproterenol beta-adrenergic receptor agonist) and the membrane permeant cAMP analogue dibutyryl-cAMP significantly increased the deposited amounts of ECM proteins at low concentrations, and this increase was reversed at higher concentrations of both agents. All these agents had the opposite effect on MMP-2 secretion, increasing it at doses where they decreased ECM protein deposition and vice versa. However, elevation of cAMP by the phosphodiesterase inhibitor IBMX had no effect either on the deposited amounts of any of the ECM proteins studied or on MMP-2 secretion. Activation of PKC by phorbol ester (PMA) resulted in a decrease in ECM protein deposition and an increase in MMP-2 secretion. Finally, chelation of intercellular calcium with BAPTA-AM resulted in an increased ECM deposition and a decrease in MMP-2 secretion. Our results show a complex pattern of regulation of ECM protein deposition by cAMP-mobilizing agents and also indicate an inverse correlation between ECM protein deposition and secretion of MMP-2. The concerted regulation of both of these processes is essential in the formation of new blood vessels, and for the integrity of the vascular wall.
Authors:
E Papadimitriou; C R Waters; V G Manolopoulos; B R Unsworth; M E Maragoudakis; P I Lelkes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endothelium : journal of endothelial cell research     Volume:  8     ISSN:  1062-3329     ISO Abbreviation:  Endothelium     Publication Date:  2001  
Date Detail:
Created Date:  2002-02-04     Completed Date:  2003-07-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9412590     Medline TA:  Endothelium     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  243-53     Citation Subset:  IM    
Affiliation:
Dept. of Pharmacy, Univ. of Wisconsin Medical School, Milwaukee, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenal Medulla / cytology*
Animals
Cell Culture Techniques
Egtazic Acid / analogs & derivatives*,  pharmacology
Endothelium / cytology*,  metabolism,  ultrastructure
Enzyme Activation
Extracellular Matrix / drug effects,  metabolism*
Extracellular Matrix Proteins / drug effects
Forskolin / pharmacology
Matrix Metalloproteinase 2 / metabolism*,  secretion
Rats
Second Messenger Systems
Tetradecanoylphorbol Acetate / pharmacology
Chemical
Reg. No./Substance:
0/Extracellular Matrix Proteins; 16561-29-8/Tetradecanoylphorbol Acetate; 66428-89-5/Forskolin; 67-42-5/Egtazic Acid; 85233-19-8/1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; EC 3.4.24.24/Matrix Metalloproteinase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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