p53 protects against alcoholic fatty liver disease via <scp>ALDH2</scp> inhibition

Yao, Pengbo; Zhang, Zhenxi; Liu, Hongchao; Jiang, Peng; Li, Wei; Du, Wenjing

doi:10.15252/embj.2022112304

Cited by 5 publications

(3 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, this function of ME2 is mediated by its product pyruvate, which directly binds to β-catenin and increases β-catenin protein levels. Our recent study reported that pyruvate directly binds to and activates acetaldehyde dehydrogenase 2 (ALDH2) [32]. Together, these findings indicate that pyruvate may have a broader range of new functions within cells in a metabolism-independent manner.…”

Section: Discussionmentioning

confidence: 93%

ME2 Promotes Hepatocellular Carcinoma Cell Migration through Pyruvate

Yang

Zhang

et al. 2023

Metabolites

Self Cite

View full text Add to dashboard Cite

Cancer metastasis is still a major challenge in clinical cancer treatment. The migration and invasion of cancer cells into surrounding tissues and blood vessels is the primary step in cancer metastasis. However, the underlying mechanism of regulating cell migration and invasion are not fully understood. Here, we show the role of malic enzyme 2 (ME2) in promoting human liver cancer cell lines SK-Hep1 and Huh7 cells migration and invasion. Depletion of ME2 reduces cell migration and invasion, whereas overexpression of ME2 increases cell migration and invasion. Mechanistically, ME2 promotes the production of pyruvate, which directly binds to β-catenin and increases β-catenin protein levels. Notably, pyruvate treatment restores cell migration and invasion of ME2-depleted cells. Our findings provide a mechanistic understanding of the link between ME2 and cell migration and invasion.

show abstract

Section: Discussionmentioning

confidence: 93%

ME2 Promotes Hepatocellular Carcinoma Cell Migration through Pyruvate

Yang

Zhang

et al. 2023

Metabolites

Self Cite

View full text Add to dashboard Cite

show abstract

“…Crosslinking was performed according to instructions of disuccinimidyl suberate (DSS) crosslinkers (Thermo Scientific, Waltham, MA, USA) [39]. Cells were collected and washed two times with ice-cold PBS.…”

Section: Disuccinimidyl Suberate (Dss) Crosslinkingmentioning

confidence: 99%

The Binding of HSPA8 and Mitochondrial ALDH2 Mediates Oxygen-Glucose Deprivation-Induced Fibroblast Senescence

Hui,

Song,

et al. 2023

Antioxidants

View full text Add to dashboard Cite

Cellular senescence refers to the permanent and irreversible cessation of the cell cycle. Recently, it has gained significant interest as a promising target for preventing cardiovascular diseases. Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that has been closely linked with an increased risk of cardiovascular diseases. In this study, bioinformatics analysis revealed that the signaling pathway for fibroblast senescence is significantly activated in mice after myocardial infarction (MI), and that ALDH2 might be a crucial molecule responsible for inducing this change. Therefore, we created an NIH3T3 fibroblast cell line oxygen-glucose deprivation (OGD) model to replicate the conditions of MI in vitro. We further revealed that decreased ALDH2 enzyme activity is a critical factor that affects fibroblast senescence after OGD, and the activation of ALDH2 can improve the mitochondrial damage caused by OGD. We identified Heat Shock 70-kDa Protein 8 (HSPA8) as an interacting protein of ALDH2 through co-immunoprecipitation (Co-IP) and mass spectrometry (MS) detection. Subsequently, our studies showed that HSPA8 translocates to the mitochondria after OGD, potentially binding to ALDH2 and inhibiting its enzyme activity. By transfecting siRNA to inhibit HSPA8 expression in cells, it was found that ALDH2 enzyme activity can be significantly increased, and the senescence characteristics induced by OGD in NIH3T3 cells can be improved. In conclusion, the data from this study suggest that HSPA8, in conjunction with ALDH2, could regulate fibroblast senescence after oxygen-glucose deprivation, providing a new direction and foundation for effectively intervening in fibroblast senescence after myocardial infarction.

show abstract

“…ADH1B*2 was associated with lower risk of alcohol consumption in Jewish and European populations. [16][17][18] On the other hand, ADH2*1 and ADH3*2 isozymes confer an increased risk of alcohol dependence in individuals with alcohol abuse, except for those with East Asian ancestry. 19 ALDH has two isoforms: ALDH1 and ALDH2.…”

Section: Genes Involved In Neurotransmission In Individuals With Alco...mentioning

confidence: 99%

Genes in Alcoholic Liver Disease: A Complex Interplay

Dawra¹,

Manrai²

2023

Gene Expr

View full text Add to dashboard Cite

Alcohol-related liver disease is a major public health problem, with a varying clinical course and often devastating consequences. Its spectrum can vary from alcohol-related fatty liver, alcoholic hepatitis, cirrhosis, and hepatocellular carcinoma. Multiple environmental, genetic, socio-economic and epigenetic factors are intrinsically involved, affecting disease behavior and progression. Recent advances in genome-wide association studies have identified multiple genetic polymorphisms that may affect the pathophysiological process, and in turn, affect disease progression. Although the present understanding of this complex process remains nascent at best, there is an ardent need to incorporate available genetic markers into diagnostic and prognostic algorithms. This may pave the way for future research into targeted therapies.

show abstract

p53 protects against alcoholic fatty liver disease via ALDH2 inhibition

Cited by 5 publications

References 45 publications

ME2 Promotes Hepatocellular Carcinoma Cell Migration through Pyruvate

ME2 Promotes Hepatocellular Carcinoma Cell Migration through Pyruvate

The Binding of HSPA8 and Mitochondrial ALDH2 Mediates Oxygen-Glucose Deprivation-Induced Fibroblast Senescence

Genes in Alcoholic Liver Disease: A Complex Interplay

Contact Info

Product

Resources

About