Overexpression of aldehyde dehydrogenase 1A1 reduces oxidation-induced toxicity in SH-SY5Y neuroblastoma cells

J Neurosci Res. 2010 Feb 15;88(3):686-94. doi: 10.1002/jnr.22230.

Abstract

Oxidative stress leading to lipid peroxidation is a problem in neurodegenerative diseases, because the brain is rich in polyunsaturated fatty acids and low in endogenous antioxidants. One of the most toxic byproducts of lipid peroxidation, 4-hydroxynonenal (HNE), is implicated in oxidative stress-induced damage in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). In this study, the human neuroblastoma cell line SH-SY5Y was used to test the protective effects of increasing the detoxification of HNE by overexpressing the HNE-detoxifying enzyme aldehyde dehydrogenase 1A1 (ALDH1). Overexpression of ALDH1 in the SH-SY5Y cells acts to reduce production of protein-HNE adducts and activation of caspase-3. Our data suggest that detoxification of HNE could be therapeutic in preventing some of the toxic disruptions of the brain's redox systems found in many neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase / metabolism*
  • Aldehyde Dehydrogenase 1
  • Aldehydes / metabolism
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Genetic Vectors
  • Humans
  • Hydrogen Peroxide / toxicity
  • Immunohistochemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Neurons / enzymology
  • Neurons / physiology
  • Oxidative Stress / physiology*
  • Retinal Dehydrogenase
  • Transfection

Substances

  • Aldehyde Dehydrogenase 1
  • Aldehydes
  • Isoenzymes
  • Hydrogen Peroxide
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase
  • CASP3 protein, human
  • Caspase 3
  • 4-hydroxy-2-nonenal