Hypochlorous acid causes caspase activation and apoptosis or growth arrestin human endothelial cells

We have investigated the effect of hypochlorous acid (HOCl) on cultured hum an umbilical-vein endothelial cells and shown that, whereas higher concentr ations cause rapid necrosis, smaller amounts of this oxidant induce apoptos is or growth arrest. Exposure to 20-40 nmol of HOCl per 1.2 x 10(5) cells i nitiated apoptosis that was determined morphologically, by the identificati on of apoptotic nuclei with Hoechst 33342, and by detection of phosphatidyl serine on the outer membrane. Degraded DNA was detected by how cytometry. H OCl induced caspase activity; specific inhibition of caspases was shown to prevent apoptosis. No caspase activation could be detected with 50 nmol of HOCl per 1.2 x 10(5) cells, a dose that caused more extensive necrosis. Low er doses of HOCl, which did not cause cell death, resulted in a transient g rowth arrest that was apparent with as little as 5 nmol of HOCl per 1.2 x 1 05 cells. These results show that HOCl can modify cellular responses that a re dependent on signal transduction pathways in a manner similar to that of other oxidants.