Incubation of endothelial cells in a superoxide-generating system: impaired low-density lipoprotein receptor-mediated endocytosis.

Endothelial cells (EC) of blood vessels are submitted to oxidative stress under various circumstances. These conditions may modify EC functions; therefore, in the present work we have studied the receptor-mediated endocytosis of low-density lipoproteins (LDL) and malondialdehyde-modified LDL by the LDL receptor and the "scavenger" receptor, respectively, in cultured human umbilical vein EC after short (0-120 minutes) incubations in a superoxide anion (O2-) generating system. In both receptor-mediated processes, the oxidative stress produces a significant decrease at four different LDL concentrations (5-50 micrograms/ml) after 120 minutes of oxidation. On the other hand, the fluid-phase endocytosis of sucrose by EC seems to be stimulated by these conditions. Furthermore, incorporation of antioxidant enzymes in the O2- -producing system shows that H2O2 is an obligatory intermediate in order to produce the effect on the receptor-mediated processes. Hypotheses concerning the mechanisms involved in the modifications of endocytotic processes and their implications in vivo are discussed.