Inhibition of prostaglandin synthesis in human endothelial cells treated with metabolic inhibitors. Biochim Biophys Acta 1992 Jan 24;1123(2):216-26
Date
01/24/1992Pubmed ID
1739750DOI
10.1016/0005-2760(92)90114-bScopus ID
2-s2.0-0026540949 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
Endothelial cell injury is often associated with increased synthesis of prostaglandin (PG)I2. We observed, however, that endothelial cells treated with metabolic inhibitors which reduce cellular ATP content develop an injury pattern characterized by reduced PGI2 synthesis. This study examined the relationship between cell injury, arachidonic acid metabolism and ATP content in human umbilical vein endothelial cells treated with 2-deoxyglucose (2DG), a glycolytic inhibitor, and oligomycin (OG), a respiratory chain inhibitor. Either inhibitor alone significantly reduced cellular ATP concentrations, but only OG reduced basal PG synthesis. The combination of 2DG and OG, however, was more effective than either agent alone in reducing cellular ATP content (greater than or equal to 50% of control) and inhibiting basal and agonist-stimulated PGI2 synthesis. This reduced PGI2 synthesis preceded 51chromium release, lactic dehydrogenase release and was not associated with a net release of arachidonic acid from cell membranes. Histamine, A23187 and bradykinin stimulated PGI2 synthesis in untreated but not in 2DG and OG treated cells. Exogenous arachidonic acid increased PGI2 synthesis to a similar extent in both 2DG and OG treated and untreated cells. Therefore, reduced PG synthesis in 2DG and OG treated endothelial cells is not due to inhibition of cyclooxygenase. Furthermore, reduced PG synthesis in these cells occurs prior to cell injury and is not strictly associated with cellular ATP depletion.
Author List
Revtyak GE, Campbell WBAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
BradykininCalcimycin
Cells, Cultured
Cyclooxygenase Inhibitors
Deoxyglucose
Endothelium, Vascular
Epoprostenol
Fatty Acids
Histamine
Humans
Oligomycins
Prostaglandin Antagonists
