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Regulation of PGE(2) and PGI(2) release from human umbilical vein endothelial cells by actin cytoskeletonDisruption of microfilaments in human umbilical vein endothelial cells (HUVEC) with cytochalasin D (cytD) or latrunculin A (latA) resulted in a 3.3- to 5.7-fold increase in total synthesis of prostaglandin E(2) (PGE(2)) and a 3.4- to 6.5-fold increase in prostacyclin (PGI(2)) compared with control cells. Disruption of the microtubule network with nocodazole or colchicine increased synthesis of PGE(2) 1.7- to 1.9-fold and PGI(2) 1.9- to 2.0-fold compared with control cells. Interestingly, however, increased release of PGE(2) and PGI(2) from HUVEC into the media occurred only when microfilaments were disrupted. CytD treatment resulted in 6.7-fold more PGE(2) and 3.8-fold more PGI(2) released from HUVEC compared with control cells; latA treatment resulted in 17.7-fold more PGE(2) and 11.2-fold more PGI(2) released compared with control cells. Both increased synthesis and release of prostaglandins in response to all drug treatments were completely inhibited by NS-398, a specific inhibitor of cyclooxygenase-2 (COX-2). Disruption of either microfilaments using cytD or latA or of microtubules using nocodazole or colchicine resulted in a significant increase in COX-2 protein levels, suggesting that the increased synthesis of prostaglandins in response to drug treatments may result from increased activity of COX-2. These results, together with studies demonstrating a vasoprotective role for prostaglandins, suggest that the cytoskeleton plays an important role in maintenance of endothelial barrier function by regulating prostaglandin synthesis and release from HUVEC.
Document ID
20040112328
Document Type
Reprint (Version printed in journal)
Authors
Sawyer, S. J. (Indiana University School of Medicine Indianapolis, Indiana 46202, United States)
Norvell, S. M.
Ponik, S. M.
Pavalko, F. M.
Date Acquired
August 21, 2013
Publication Date
September 1, 2001
Publication Information
Publication: American journal of physiology. Cell physiology
Volume: 281
Issue: 3
ISSN: 0363-6143
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: AR-45218
CONTRACT_GRANT: AR-45831
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Cell Biology