ALDH2 Knockout Induces Dysregulation of Arginine biosynthesis in SKBR-3 Breast Cancer Cells
Background/Objectives: Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, mitigates cellular stress by detoxifying reactive aldehydes produced during alcohol exposure and endogenous metabolic processes. ALDH2*2 polymorphism, which results in deficient catalytic activity, is prevalent in East Asian populations and is associated with an increased risk of cancer and other diseases. While the…
Background: Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that helps mitigate cellular stress by detoxifying reactive aldehydes. Individuals with ALDH2*2 polymorphism, which leads to reduced catalytic activity, are more likely to develop cancer and other diseases. The metabolic dysregulations caused by ALDH2 deficiency have not been extensively studied.
Methods: Researchers created an ALDH2 knockout subline of SKBR-3 cells using the CRISPR/Cas9 strategy. The metabolomic profiles of the control (SKBR-3/C) and ALDH2 knockout (SKBR-3/ADKO) cells were assessed through ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS).
Results: The ALDH2 knockout in SKBR-3 cells led to increased cellular stress, with elevated levels of 8-OHdG, reactive oxygen species (ROS), and malondialdehyde (MDA). A total of 5,033 signals were analyzed, with 281 significantly different (fold change ≥ 2, p-value).
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