INDUCTION OF APOPTOSIS AND SECONDARY NECROSIS IN RAT DORSAL-ROOT GANGLION-CELL CULTURES BY OXIDIZED LOW-DENSITY-LIPOPROTEIN

Neural cell degeneration underlies central and peripheral nervous syst em disorders. In this study we examined the influence of oxidized low density lipoprotein (Ox-LDL) on rat dorsal root ganglion (DRG) cells i n culture. Methods used were cell morphology, lactate dehydrogenase (L DH) release, the TUNEL-reaction and DNA fragmentation. Exposure of DRG cells to Ox-LDL for 24 h led to elevation of LDH in the culture mediu m; short term exposure (4 h) induced apoptosis, evidenced by DNA fragm entation and a positive TUNEL-reaction. DRG cells modified LDL in the presence of Cu2+ to mildly oxidized and to a small extent to fully oxi dized forms; these in situ-generated LDL oxidation products were stron gly toxic. These results suggest that Ox-LDL is a neurotoxin; it initi ates apoptotic cell injury which progresses to necrosis and cell death .