The capacity of formaldehyde, a chemical frequently used in manufactured goods such as automotive parts and wood products, to damage DNA, interfere with cell replication and cause cancer inspired new federal regulations this summer. But a new study in the American Journal of Pathology finds that the substance may pose a broader threat to health than previously thought by injuring cells in another way.
"We think formaldehyde is a much more dangerous toxicant in the sense that it is not only damaging DNA but there is also extensive damage to proteins," said corresponding author. "On one hand, damage to proteins in the nucleus could impair the stress responses to and repair of DNA damage, and on the other hand accumulation of damaged proteins could contribute directly to malfunctioning and killing of cells."
The findings may substantiate questions about whether formaldehyde adversely affects the nervous system, as has been seen in some animal studies, author said.
In several experiments described in the new paper, the team at Brown showed that exposure of three types of human lung cells to formaldehyde set off a sequence of damage and cellular responses similar to what happens when cells are exposed to excessive heat. They saw tell-tale indications of widespread accumulation of damaged proteins. These indications were the appearance of a specific set of protective processes that try to clean up the damaged proteins before their buildup could kill the cells.
In the new study lead author looked for signs of protein damage and saw them clearly. They observed that after brief formaldehyde exposures, cells exhibited a massive polyubiquitination, a process of marking damaged proteins for disposal, lest they accumulate. Shortly after the polyubiquitination process began, they then observed the heat shock response as a new set of proteins joined the massive cleanup effort.
Ultimately many of the cells died, despite the activation of cell's defense responses. In an experiment where they purposely disabled one of the key heat shock response proteins, cells were even more likely to die.
Neither the polyubiquitination response nor the heat shock response occurred in control cells that did not have any contact with formaldehyde. Meanwhile, the scientists also subjected cells to substances known to damage DNA but not proteins, and found that this didn't unleash the polyubiquitination or heat shock responses. That suggests that those reactions were not responses to formaldehyde's DNA damage.
Senior author said the findings might explain why formaldehyde may be toxic to the nervous system. Neurons don't divide or replicate DNA, so they aren't as vulnerable to the kind of damage formaldehyde does to DNA. But they are especially vulnerable to accumulations of damaged and misfolded proteins – that's what happens in Alzheimer's and some other disease, for example – and that's exactly what Zhitkovich's team has found formaldehyde causes in cells. Animal studies, he noted, have shown that formaldehyde exposure undermines brain functions such as memory and learning.
To directly test this hypothesis, his group has begun formaldehyde exposure experiments with human neurons in the lab, author said.
The team is also investigating whether formaldehyde damages particular types of proteins or whether it is toxic to them across the board.
https://news.brown.edu/articles/2016/09/formaldehyde
Formaldehyde damages proteins, not just DNA
- 1,484 views
- Added
Edited
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
Chronic lung disease can increase severity of COVID
Read more
Microbiome and plant-based diet may protect against multiple sclerosis
Read more
Antibiotics in early life could affect brain gene expression
Read more
Why second dose of COVID-19 vaccine shouldn't be skipped
Read more
Neurogenesis from gut microbe secreted molecule
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar