Dataset Information

Expression data from ALDH2 knockdown in head and neck cancer cells.

ABSTRACT: We demonstrate that ALDH2 knockdown increased multiple canonical pathways and transcriptions factors We used microarrays to analyze the potential mechanism by which ALDH2 regulates gene expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253622 | GEO | 2025/02/19

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Obesity and type 2 diabetes have reached pandemic proportion. In particular, the population with diabetes is expected to rise rapidly in East and South Asia. ALDH2 (acetaldehyde dehydrogenase 2, mitochondrial) is the key metabolizing enzyme of acetaldehyde and other toxic aldehydes, such as 4-hydroxynonenal (4-HNE). A missense Glu504Lys mutation of the ALDH2 gene is prevalent in 560 million East Asians, resulting in reduced ALDH2 enzymatic activity. We found that Aldh2 knock-in (KI) mice mimicking human Glu504Lys mutation were prone to develop diet-induced obesity, glucose intolerance, insulin resistance, and fatty liver compared with controls due to reduced adaptive thermogenesis and energy expenditure. We found elevated 4-HNE levels and increased 4-HNE adducted proteins due to reduced activity of ALDH2 of the brown adipose tissue (BAT) from the Aldh2 homozygous KI mice. Proteomic analyses of the BAT from the Aldh2 KI mice identified increased 4-HNE-adducted proteins involved in mitochondrial fatty acid oxidation (FAO) and electron transport chain (ETC), leading to markedly decreased FAO and mitochondrial respiration of BAT, which is essential for adaptive thermogenesis and energy expenditure. AD-9308 is a water-soluble prodrug of a potent and highly selective ALDH2 activator AD-5591. In vitro, AD-5591 enhanced both WT and mutant ALDH2 enzymatic activities. AD-9308 allosterically activates ALDH2 mainly by partially blocking the substrate exit tunnel, thereby accelerating the substrate-enzyme collision.4-HNE-adducted proteins, especially those involved in mitochondrial fatty acid beta-oxidation and electron transfer chain of the brown adipose tissue from the Aldh2 knock-in mice, leading to impaired mitochondrial dysfunction brown adipose tissue. In vivo, AD-9308 treatment reduced serum 4-HNE levels, ameliorated diet-induced obesity and fatty liver, and improved glucose homeostasis in both Aldh2 WT and KI mice dose-dependently. Our data highlight the therapeutic potential of reducing toxic aldehyde levels by activating ALDH2 for treating metabolic diseases.

Dataset Information

Expression data from ALDH2 knockdown in head and neck cancer cells.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets