Antioxidants inhibit the human cortical neuron apoptosis induced by hydrogen peroxide, tumor necrosis factor alpha, dopamine and beta-amyloid peptide 1-42.
Several substances related to the neurodegenerative diseases of Alzheimer and Parkinson, such as hydrogen peroxide, tumor necrosis factor alpha, dopamine and beta-amyloid peptide 1-42, have been shown to induce apoptosis in tumoral cell lines and rat neurons but not in human neurons. Moreover, the role of mitochondria (membrane potential) during neuronal apoptosis is still a matter of debate. We present here, for the first time, in cultured human cortical neurons that the DNA fragmentation induced by these substances was preceded by a decrease of the mitochondrial membrane potential. We have also examined the antiapoptotic effect of the antioxidants glutathione, N-acetyl-cysteine and ascorbic acid. All these antioxidants inhibited the apoptosis induced by hydrogen peroxide, tumor necrosis factor alpha, dopamine and beta-amyloid peptide 1-42, since they were able to inhibit completely the mitochondrial membrane potential depolarization and the DNA fragmentation.
Medina
Sonia
S
Department of Clinical Biochemistry, Hospital Universitario La Paz, Castellana 261, 28046, Madrid, Spain.
Martínez
Marcos
M
Hernanz
Angel
A
D000111:Acetylcysteine / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology*; D004298:Dopamine / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology; D009474:Neurons / Q000473:pathology*; D010446:Peptide Fragments / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D016166:Free Radical Scavengers; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D006861:Hydrogen Peroxide; D005978:Glutathione; D001205:Ascorbic Acid; D004298:Dopamine; D000111:Acetylcysteine