Lactosylceramide mediates shear-induced endothelial superoxide production and intercellular adhesion molecule-1 expression

Li Hong Yeh, Adam M. Kinsey, Subroto Chatterjee, B. Rita Alevriadou

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Laminar shear stress activates NADPH oxidase in vascular endothelial cells (ECs), and the generated superoxide radicals (O2·-) are known to be involved in intercellular adhesion molecule (ICAM)-1 expression. In this study, the role of a glycosphingolipid (GSL), lactosylceramide (LacCer), as a second messenger in the shear-induced O2·- generation and ICAM-1 expression was examined. It is known that glucosylceramide synthase (GlcT-1) catalyzes the synthesis of glucosylceramide (GlcCer) from ceramide, and subsequently lactosylceramide synthase (GalT-2) synthesizes LacCer from GlcCer. We observed that exposing cultured human umbilical vein ECs (HUVECs) to fluid shear stress (20 dyn/cm2 for 30 min) activated GalT-2. Shear stress also increased EC O2·- generation, that peaked at 30 min, and surface ICAM-1 protein expression at 6 h post-shear. EC preincubation with the antioxidant N-acetylcysteine (NAC; 20 mM for 2 h) completely abolished the shear-induced O2·- production and significantly inhibited ICAM-1 expression. EC preincubation with D-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of the GSL glycosyltransferases GlcT-1 and GalT-2, abrogated the shear-induced activation of GalT-2. D-PDMP also abolished the shear-induced O2·- production and ICAM-1 expression. We conclude that laminar shear stress activates GalT-2 to produce LacCer. In turn, LacCer activates NADPH oxidase, which produces O2·-, and O2·- mediates the shear-induced increase in ICAM-1 expression. Thus, LacCer may play an important role in hemodynamic force-induced pathological conditions, such as atherosclerosis and ischemia/reperfusion injury.

Original languageEnglish (US)
Pages (from-to)551-559
Number of pages9
JournalJournal of Vascular Research
Issue number6
StatePublished - 2001


  • Endothelial cell
  • Glycosphingolipid
  • ICAM-1
  • Lactosylceramide
  • Reactive oxygen species
  • Shear stress

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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