Sphingomyelinase and cell-permeable ceramide analogs increase the release of plasminogen activator inhibitor-1 from cultured endothelial cells

Thrombosis Research
S SoedaA Nagamatsu

Abstract

We investigated the effect of exogenous staphylococcal sphingomyelinase (SMase) on the release of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) from cultured human umbilical vein endothelial cells (HUVEC). Addition of SMase (2 units/ml) to the culture medium induced an approx. 15-fold increase in the extracellular level of PAI-1 antigen at 3 h. No significant increase in the level of t-PA antigen was detected. Treatment of HUVEC with SMASE (2 units/ml) for 3 h resulted in a significant decrease in the cellular sphingomyelin (SM) level, accompanied by a corresponding increase in the ceramide level. Cell-permeable ceramide analogs also enhanced the release of PAI-1 from cultured HUVEC in concentration- and time-dependent manners. A 6-fold increase in PAI-1 antigen level was observed after incubation for 3 h with 10 microM N-acetylsphingosine. Similar effect was noted as early as 2 h with 10 microM N-hexyanoylsphingosine. Addition of sphingosine failed to affect the release of PAI-1 from cultured HUVEC, indicating that the effects of ceramide analogs were independent of sphingosine generation. Pretreatment with cycloheximide or actinomycin D abated the response of HUVEC to N-acetylsphingosi...Continue Reading

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Citations

May 9, 2000·Progress in Lipid Research·N AugéT Levade
Apr 24, 2008·Critical Care Medicine·Claudia C dos SantosMingyao Liu
May 14, 2009·American Journal of Physiology. Endocrinology and Metabolism·Guang YangFahumiya Samad
Oct 19, 2006·Experimental and Molecular Pathology·Saumya PandeyDevendra K Agrawal
Jun 26, 2004·Circulation Research·Rinky BhatiaCharles J Lowenstein
Nov 22, 2001·Circulation Research·T LevadeR Salvayre
Dec 15, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Erich Gulbins, Pin Lan Li
Nov 24, 2016·Frontiers in Neuroscience·Rolando I CastilloPablo A Gaspar

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