Oxidized high-density lipoprotein induces neuron death.
High-density lipoprotein (HDL) exists within the brain and is highly vulnerable to oxidative modifications. The focus of the present study was to determine the effect of HDL and oxidized HDL (oxHDL) upon neurons, astrocytes, and microglia. Administration of highly oxidized HDL, but not native, minimally, or moderately modified HDL resulted in a dose- and time-dependent increase in oxidative stress and death of cultured rat embryonic neurons. Astrocyte and microglia cultures treated with highly oxidized HDL displayed increased reactive oxygen species formation but no toxicity. Application of oxHDL exacerbated oxidative stress and neuron death induced by beta-amyloid peptide. Studies using pharmacological inhibitors implicate the involvement of calcium and reactive oxygen species in oxHDL-induced neuronal loss. Neural cells expressing increased levels of BCL-2 had decreased levels of oxidative stress and neuron death following exposure to oxHDL. Together, these data demonstrate that oxHDL increases oxidative stress in neurons, astrocytes, and microglia which ultimately culminate in neuron death.
Keller
J N
JN
Department of Biochemistry, Sanders-Brown Center on Aging, Lexington, Kentucky, 40536, USA.
Hanni
K B
KB
Kindy
M S
MS
D016564:Amyloid beta-Protein Precursor / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000633:toxicity*; D017628:Microglia / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016564:Amyloid beta-Protein Precursor; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D019253:Proto-Oncogene Proteins c-bcl-2; C099252:oxidized low density lipoprotein; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid