Regulation of PGE(2) and PGI(2) release from human umbilical vein endothelial cells by actin cytoskeleton |
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Authors: | Sawyer S J Norvell S M Ponik S M Pavalko F M |
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Institution: | Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. |
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Abstract: | Disruption of microfilaments in human umbilical vein endothelialcells (HUVEC) with cytochalasin D (cytD) or latrunculin A (latA)resulted in a 3.3- to 5.7-fold increase in total synthesis ofprostaglandin E2 (PGE2) and a 3.4- to 6.5-foldincrease in prostacyclin (PGI2) compared with controlcells. Disruption of the microtubule network with nocodazole orcolchicine increased synthesis of PGE2 1.7- to 1.9-fold andPGI2 1.9- to 2.0-fold compared with control cells.Interestingly, however, increased release of PGE2 andPGI2 from HUVEC into the media occurred only when microfilaments were disrupted. CytD treatment resulted in 6.7-fold morePGE2 and 3.8-fold more PGI2 released from HUVECcompared with control cells; latA treatment resulted in 17.7-fold more PGE2 and 11.2-fold more PGI2 released comparedwith control cells. Both increased synthesis and release ofprostaglandins in response to all drug treatments were completelyinhibited by NS-398, a specific inhibitor of cyclooxygenase-2 (COX-2).Disruption of either microfilaments using cytD or latA or ofmicrotubules using nocodazole or colchicine resulted in a significantincrease in COX-2 protein levels, suggesting that the increasedsynthesis of prostaglandins in response to drug treatments may resultfrom increased activity of COX-2. These results, together with studies demonstrating a vasoprotective role for prostaglandins, suggest thatthe cytoskeleton plays an important role in maintenance of endothelialbarrier function by regulating prostaglandin synthesis and release from HUVEC. |
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