The concept of “aldehyde load” in neurodegenerative mechanisms: Cytotoxicity of the polyamine degradation products hydrogen peroxide, acrolein, 3-aminopropanal, 3-acetamidopropanal and 4-aminobutanal in a retinal ganglion cell line

• Published in: Brain research Vol. 1145; pp. 150 - 156
• Main Authors: Wood, Paul L, Khan, M. Amin, Moskal, Joseph R
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 11.05.2007; Amsterdam Elsevier; New York, NY
• Subjects: 3-Acetamidopropanal; 3-Aminopropanal; 4-Aminobutanal; Acrolein - metabolism; Acrolein - toxicity; Aldehyde dehydrogenase; Aldehyde Dehydrogenase - metabolism; Aldehyde load; Aldehydes - metabolism; Aldehydes - toxicity; Animals; beta-Alanine - metabolism; Biogenic Polyamines - metabolism; Biogenic Polyamines - toxicity; Biological and medical sciences; Brain Chemistry - physiology; Cell Death - drug effects; Cell Death - physiology; Cell Line; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Hydrogen Peroxide - toxicity; Lysosomes; Metabolic Clearance Rate - physiology; Nerve Degeneration - chemically induced; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Neurodegeneration; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - physiopathology; Neurology; Neurotoxins - metabolism; Neurotoxins - toxicity; Polyamines; Propylamines - metabolism; Propylamines - toxicity; Rats; Retinal ganglion cell; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - metabolism; Vertebrates: nervous system and sense organs; β-alanine; 3-Aminopropanal; Hydrogen peroxide; β-alanine; Neurodegeneration; Aldehyde load; 3-Acetamidopropanal; 4-Aminobutanal; Lysosomes; Polyamines; Aldehyde dehydrogenase; Retinal ganglion cell; Polyamine; Enzyme; Alanine dehydrogenase; Lysosome; ); Cytotoxicity; Retina; Aldehyde; Eye; Visual system; Cell line; Neurodegeneration Aldehyde load Polyamines 3-Aminopropanal 3-Acetamidopropanal 4-Aminobutanal Hydrogen peroxide Retinal ganglion cell Lysosomes p-alanine Aldehyde dehydrogenase; Aldehyde dehydrogenase (NAD; Degeneration; Oxidoreductases
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.10.004

Abstract In neurodegenerative diseases augmented polyamine metabolism results in the generation of hydrogen peroxide and a number of reactive aldehydes that participate in the death of compromised tissue. The major aldehydes produced by polyamine oxidase and amine oxidases include the 2-alkenal acrolein, the acetoamidoaldehyde 3-acetamidopropanal (3-AAP) and the aminoaldehydes 3-aminopropanal (3-AP) and 4-aminobutanal (4-AB). Using retinal ganglion cell (E1A-NR.3) cultures, we confirmed the cytotoxicity of acrolein and 3-AP. For the first time we also demonstrated the cytotoxicity of 4-AB and the lack of toxicity of 3-AAP. Our data with 3-AAP, a product of N-acetylspermine and N-acetylspermidine metabolism, indicate that the aldehyde function of aminoaldehydes is insufficient to express toxicity since the free amino group of aminoaldehydes is also required to gain access to lysosomes where their cytotoxic actions are expressed via leakage of cathepsins that compromise mitochondrial integrity. Metabolism of 3-AP to β-alanine by aldehyde dehydrogenase was also evaluated in retinal ganglion cell cultures and found to proceed at a linear rate of 24.3 ± 1 nmol/mg protein/h. These are the first data demonstrating the dynamic cellular detoxification of 3-AP by neural cells and support the concept that decrements in aldehyde elimination leading to an increase in “aldehyde load” may play pivotal roles in the development and progression of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis and Parkinson's disease.