Anatoly Zhitkovich, Ph.D.
An NIEHS-funded researcher and colleagues report that formaldehyde not only damages DNA but can also cause extensive damage to proteins. New federal regulations limiting formaldehyde emissions from composite wood products were passed earlier this year after the chemical was found to damage DNA, interfere with cell replication, and cause cancer.
To find out whether formaldehyde can directly damage proteins, the researchers examined the responses of three different types of human lung cells to formaldehyde. They looked for polyubiquitinated proteins because cells use polyubiquitin to mark damaged proteins that need to be broken down for removal. In all three cell types, the researchers observed large amounts of polyubiquitinated proteins in the cell nucleus and cytoplasm, indicating high levels of protein damage.
Shortly after polyubiquitination began, the researchers observed a cell response similar to what happens when cells are exposed to excessive heat. This response indicated that the cell’s protective mechanisms were trying to clean up the damaged proteins before they accumulated enough to kill the cells. Ultimately many of the cells died, despite the activation of cell’s defense responses. When the researchers disabled one of the key heat shock response proteins, cells were even more likely to die.
The researchers say that their results indicate that formaldehyde is strongly damaging to proteins, which helps explain the diverse effects observed with formaldehyde exposure.
Citation: Ortega-Atienza S, Rubis B, McCarthy C, Zhitkovich A. 2016. Formaldehyde Is a potent proteotoxic stressor causing rapid heat shock factor protein 1 activation and lys48-linked polyubiquitination of proteins. Am J Pathol 186(11):2857-2868.