Aldehyde dehydrogenase 2 deficiency reinforces formaldehyde-potentiated pro-inflammatory responses and glycolysis in macrophages.
J Biochem Mol Toxicol
; 38(1): e23518, 2024 Jan.
Article
en En
| MEDLINE
| ID: mdl-37638564
ABSTRACT
Aldehyde dehydrogenase 2 (ALDH2) deficiency caused by genetic variant is present in more than 560 million people of East Asian descent, which can be identified by apparent facial flushing from acetaldehyde accumulation after consuming alcohol. Recent findings indicated that ALDH2 also played a critical role in detoxification of formaldehyde (FA). Our previous studies showed that FA could enhance macrophagic inflammatory responses through the induction of HIF-1α-dependent glycolysis. In the present study, pro-inflammatory responses and glycolysis promoted by 0.5 mg/m3 FA were found in mice with Aldh2 gene knockout, which was confirmed in the primary macrophages isolated from Aldh2 gene knockout mice treated with 50 µM FA. FA at 50 and 100 µM also induced stronger dose-dependent increases of pro-inflammatory responses and glycolysis in RAW264.7 murine macrophages with knock-down of ALDH2, and the enhanced effects induced by 50 µM FA was alleviated by inhibition of HIF-1α in RAW264.7 macrophages with ALDH2 knock-down. Collectively, these results clearly demonstrated that ALDH2 deficiency reinforced pro-inflammatory responses and glycolysis in macrophages potentiated by environmentally relevant concentration of FA, which may increase the susceptibility to inflammation and immunotoxicity induced by environmental FA exposure.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Etanol
/
Acetaldehído
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biochem Mol Toxicol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
TOXICOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China