ReferenceID 1079
Acetaldehyde induces phosphorylation of dynamin-related protein 1 and mitochondrial dysfunction via elevating intracellular ROS and Ca2+ levels
Redox Biol
Excessive alcohol consumption impairs brain function and has been associated with an earlier onset of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Acetaldehyde, the most toxic
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Record Fields
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- Reference Id
- 1079
- Evidence Id
- 17669
- Core Evidence Id
- 17669
- Source Reference Id
- 2146
- Herb2 Reference Id
- HBREF002943
- Subject Paper Key
- HBIN014388_31756635
- Pubmed Id
- 31756635
- Doi
- 10.1016/j.redox.2019.101381
- Paper Title
- Acetaldehyde induces phosphorylation of dynamin-related protein 1 and mitochondrial dysfunction via elevating intracellular ROS and Ca2+ levels
- Paper Abstract
- Excessive alcohol consumption impairs brain function and has been associated with an earlier onset of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Acetaldehyde, the most toxic metabolite of alcohol, has been speculated to mediate the neurotoxicity induced by alcohol abuse. However, the precise mechanisms by which acetaldehyde induces neurotoxicity remain elusive. In this study, it was found that acetaldehyde treatment induced excessive mitochondrial fragmentation, impaired mitochondrial function and caused cytotoxicity in cortical neurons and SH-SY5Y cells. Further analyses showed that acetaldehyde induced the phosphorylation of mitochondrial fission related protein dynamin-related protein 1 (Drp1) at Ser616 and promoted its translocation to mitochondria. The elevation of Drp1 phosphorylation was partly dependent on the reactive oxygen species (ROS)-mediated activation of c-Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), as N-acetyl-l-cysteine (NAC) pretreatment inhibited the activation of JNK and p38 MAPK while attenuating Drp1 phosphorylation in acetaldehyde-treated cells. In addition, acetaldehyde treatment elevated intracellular Ca2+ level and activated Ca2+/calmodulin-dependent protein kinase II (CaMKII). Pretreatment of CaMKII inhibitor prevented Drp1 phosphorylation in acetaldehyde-treated cells and ameliorated acetaldehyde-induced cytotoxicity, suggesting that CaMKII was a key effector mediating acetaldehyde-induced Drp1 phosphorylation and mitochondrial dysfunction. Taken together, acetaldehyde induced cytotoxicity by promoting excessive Drp1 phosphorylation and mitochondrial fragmentation. Both ROS and Ca2+-mediated signaling pathways played important roles in acetaldehyde-induced Drp1 phosphorylation. The results also suggested that prevention of oxidative stress by antioxidants might be beneficial for preventing neurotoxicity associated with acetaldehyde and alcohol abuse.
- Journal
- Redox Biol
- Publish Year
- 2020
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Alzheimer's Disease; Neurotoxicity; Neurodegenerative Diseases; Parkinson's Disease; Mitochondrial Dysfunction
- Paper Title Cn
- Paper Title En
- Acetaldehyde induces phosphorylation of dynamin-related protein 1 and mitochondrial dysfunction via elevating intracellular ROS and Ca2+ levels
- Bilingual Status
- semi_complete