Oxidized high-density lipoprotein induces neuron death

High-density lipoprotein (HDL) exists within the brain and is highly vulner able to oxidative modifications. The focus of the present study was to dete rmine the effect of HDL and oxidized HDL (oxHDL) upon neurons, astrocytes, and microglia. Administration of highly oxidized HDL, but not native, minim ally or moderately modified HDL resulted in a dose- and time-dependent incr ease in oxidative stress and death of cultured rat embryonic neurons. Astro cyte and microglia cultures treated with highly oxidized HDL displayed incr eased reactive oxygen species formation but no toxicity. Application of oxH DL exacerbated oxidative stress and neuron death induced by beta-amyloid pe ptide. Studies using pharmacological inhibitors implicate the involvement o f calcium and reactive oxygen species in oxHDL-induced neuronal loss. Neura l cells expressing increased levels of BCL-2 had decreased levels of oxidat ive stress and neuron death following exposure to oxHDL. Together, these da ta demonstrate that oxHDL increases oxidative stress in neurons, astrocytes , and microglia which ultimately culminate in neuron death.(C) 2000 Academi c Press.