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

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.

Lessons from common markers of tumor-initiating cells in solid cancers

“…2). As for the case of CD133 and very much in accordance with its role in detoxification, ALDH1 is also up-regulated as a result of cellular stress [97]. Nonetheless, the relative proportion of ALDH1 high but not of CD44 ?…”

Monensin Is a Potent Inducer of Oxidative Stress and Inhibitor of Androgen Signaling Leading to Apoptosis in Prostate Cancer Cells

“…We have previously shown that prostate cancer cells are sensitive to ALDH inhibitor disulfiram (4). Overexpression of ALDH 1A1 has been shown to reduce oxidation-induced toxicity in neuroblastoma cells (53). Recently, ALDH 1A1 has also been identified as a marker for malignant prostate stem cells and predictor of outcome for prostate cancer patients (54,55).…”

Aldehyde dehydrogenase (ALDH) in Alzheimer’s and Parkinson’s disease

“…Several reports have pointed to the toxic effect of HNE and in particularly the conjugated form protein-HNE adducts (Zhang et al 2010). Moreover, protein-HNE adducts were found to increase in CSF and dopaminergic neurons in the SN in PD and colocalize in Lewy-bodies in neocortical and brain-stem neurons in both PD and in diffused Lewy body disease (DLBD) (Zhang et al 2010).…”

“…Moreover, protein-HNE adducts were found to increase in CSF and dopaminergic neurons in the SN in PD and colocalize in Lewy-bodies in neocortical and brain-stem neurons in both PD and in diffused Lewy body disease (DLBD) (Zhang et al 2010). In addition, increased free HNE was found in the hippocampus and amygdala of AD brains compared to controls and protein-HNE adducts are associated with neurofibrillary tangles (Zhang et al 2010). Therefore, the protective effect of overexpression of ALDH1A1 in SH-SY5Y cells via reduction of HNE was investigated (Zhang et al 2010).…”