S-Nitrosation In Endothelium: Different Outcomes Of Nrf2 And GSNOR Loss

Aging Pathway
The study reveals that the loss of the protective protein NRF2 in cells lining blood vessels leads to premature aging and increased S-nitrosation, a type of protein modification, while the loss of the enzyme GSNOR, which removes S-nitrosation, does not result in the same aging, highlighting that the context of S-nitrosation is crucial for cell fate.
Author

Gemini

Published

December 9, 2025

Our blood vessels are lined by special cells called endothelial cells, which play a vital role in keeping our cardiovascular system healthy. When these cells age prematurely, it can contribute to various heart and blood vessel diseases. Scientists are constantly working to understand what causes this aging and how to prevent it.

One important process in cells is called S-nitrosation, where a small molecule called nitric oxide attaches to proteins, changing their function. Think of it like a temporary “on” or “off” switch for proteins. This process is normally tightly controlled.

Researchers investigated two key players involved in this delicate balance: NRF2 and GSNOR. NRF2 is a protein known for its protective role, helping cells defend against stress and damage. GSNOR is an enzyme that acts like an “eraser,” removing S-nitrosation from proteins.

Surprisingly, the study found that when endothelial cells lacked NRF2, they aged prematurely and showed a significant increase in S-nitrosation. This suggests that NRF2 is crucial for preventing early aging and maintaining the proper balance of S-nitrosation. However, when the “eraser” enzyme GSNOR was missing, and S-nitrosation levels also increased, the cells did not experience the same premature aging. This indicates that simply having more S-nitrosation isn’t the whole story.

The key takeaway is that the context of S-nitrosation matters. It’s not just about the overall amount of this protein modification, but which specific proteins are modified and how these modifications occur that ultimately determine whether a cell ages prematurely or remains healthy. These findings are important because they deepen our understanding of how endothelial cells age and could open new avenues for developing treatments for cardiovascular diseases by targeting specific S-nitrosation pathways.


Source: link to paper