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 system disorders. In this study we examined the influence of oxidized low density lipoprotein (Ox-LDL) on rat dorsal root ganglion (DRG) cells in culture. Methods used were cell morphology, lactate dehydrogenase (LDH) 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 medium; short term exposure (4 h) induced apoptosis, evidenced by DNA fragmentation and a positive TUNEL-reaction. DRG cells modified LDL in the presence of Cu2+ to mildly oxidized and to a small extent to fully oxidized forms; these in situ-generated LDL oxidation products were strongly toxic. These results suggest that Ox-LDL is a neurotoxin; it initiates apoptotic cell injury which progresses to necrosis and cell death.