Asset Details
Do you wish to reserve the book?
Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity
Do you wish to request the book?
Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Endogenous formaldehyde scavenges cellular glutathione resulting in redox disruption and cytotoxicity
2022
Overview
Formaldehyde (FA) is a ubiquitous endogenous and environmental metabolite that is thought to exert cytotoxicity through DNA and DNA-protein crosslinking, likely contributing to the onset of the human DNA repair condition Fanconi Anaemia. Mutations in the genes coding for FA detoxifying enzymes underlie a human inherited bone marrow failure syndrome (IBMFS), even in the presence of functional DNA repair, raising the question of whether FA causes relevant cellular damage beyond genotoxicity. Here, we report that FA triggers cellular redox imbalance in human cells and in
Caenorhabditis elegans
. Mechanistically, FA reacts with the redox-active thiol group of glutathione (GSH), altering the GSH:GSSG ratio and causing oxidative stress. FA cytotoxicity is prevented by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), which metabolizes FA-GSH products, lastly yielding reduced GSH. Furthermore, we show that GSH synthesis protects human cells from FA, indicating an active role of GSH in preventing FA toxicity. These findings might be relevant for patients carrying mutations in FA-detoxification systems and could suggest therapeutic benefits from thiol-rich antioxidants like N-acetyl-L-cysteine.
Formaldehyde (FA) is known to exert cytotoxicity through DNA damage. Here, the authors show that FA also triggers cellular redox imbalance by reacting with glutathione (GSH), and that FA cytotoxicity is prevented by GSH synthesis and by ADH5, an enzyme that metabolizes FA-GSH products.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/109
/ 13/2
/ 13/31
/ 14
/ 14/1
/ 14/10
/ 14/34
/ 14/35
/ 42/41
/ 9/10
/ 96
/ 96/44
/ Aldehyde Oxidoreductases - genetics
/ Aldehyde Oxidoreductases - metabolism
/ Anemia
/ Animals
/ Caenorhabditis elegans Proteins - genetics
/ Caenorhabditis elegans Proteins - metabolism
/ Damage
/ DNA
/ Enzymes
/ Fanconi Anemia Complementation Group D2 Protein - genetics
/ Fanconi Anemia Complementation Group D2 Protein - metabolism
/ Humanities and Social Sciences
/ Humans
/ Mutation
/ Repair
/ Science
/ Toxicity
