So, what actually happens in the salivary glands when they stop working properly?
- The exact molecular processes inside the glands during these conditions have remained complex to map, says Golnaz Golnarnik, a researcher at the Department of Oral Biology, Faculty of Dentistry, University of Oslo.
In her doctoral research, she investigated what happens inside salivary gland acinar cells when oxidative stress disrupts their normal cellular processes.
When cells fall out of balance
Oxidative stress happens when the cell's natural defense system gets overwhelmed.
- In simple terms, it is an imbalance, she explains. - As cells do their normal metabolism, or when they face stressors like radiation or inflammation, they naturally produce reactive oxygen species. These are highly reactive molecules that can cause damage. Normally, our cells have built-in antioxidant systems that act as a defense shield to neutralize reactive oxygen species and keep cells safe.
However, when this balance is disrupted and reactive oxygen species accumulate faster than the antioxidants can clear them, the cell enters a state of oxidative stress. This excess then damages essential parts of the cell.
- In patients with conditions such as Sjögren's syndrome, diabetes, or after radiation therapy, we see this increased oxidative stress. We believe this may be an important reason why salivary glands stop functioning properly and produce less saliva, she says.
Calcium, a key to saliva production
One of the most important processes Golnarnik has investigated is how calcium signaling inside cells is affected by oxidative stress.
- Saliva production is a very finely tuned process, she explains. It is controlled by the nervous system through small changes in calcium levels inside the cells."
These calcium signals act like switches that tell the cells when to produce and secrete saliva.
- If these signals are disrupted, the cells may lose their ability to function normally, she says.
Major differences between salivary glands
In the study, Golnarnik compared two of the body's main salivary glands: the parotid gland (near the ears) and the submandibular gland (under the jaw).
- It is often presumed that major salivary glands react the same way, but our data demonstrate clear, gland-specific vulnerabilities, she says.
By inducing oxidative stress in rat acinar cell lines from both glands, she was able to observe how they responded.
The results were striking:
- Cells from the parotid gland were more vulnerable. We observed a reduction in key components, such as receptors and calcium channels that are essential for calcium signaling. she says.
When calcium signaling is weakened, the cells lose their ability to coordinate the ion transport needed to produce saliva.
At the same time, parotid gland acinar cells showed less favorable changes in their metabolism.
A more resilient gland
Cells from the submandibular gland, however, responded differently.
- They were more resistant, says Golnarnik. - They were better able to maintain calcium signaling and at the same time strengthened their antioxidant defenses.
In addition, they adjusted their metabolism in ways that appeared to protect their function.
- This suggests that submandibular gland is better equipped to adapt to stress than parotid gland, she says.
Mapping thousands of molecules
To understand what was happening inside the cells, Golnarnik used advanced techniques such as proteomics and metabolomics.
- These methods allow us to analyze large parts of proteins and metabolic molecules at once, she explains.
This made it possible to identify which biological pathways were most affected by oxidative stress, including those linked to calcium regulation, energy production, protein defenses, and key metabolic pathways.
Important basic research
The study was conducted on rat parotid and submandibular gland acinar cell lines in the laboratory, and the findings cannot yet be directly applied to patients.
- This is basic research, Golnarnik emphasizes. - The next step is to test these findings in more complex models, and eventually in human-derived cells."
Even so, this type of research is essential.
- We need this baseline knowledge to develop targeted treatments, she says. - Without mapping these cellular mechanisms, we cannot move forward.
One step closer to better treatment
In the long term, these findings could pave the way for new strategies to protect healthy salivary glands from the side effects of radiation therapy.
- If we can find ways to strengthen cellular defense mechanisms such as boosting antioxidant defenses or preserving calcium signaling, we may be able to protect gland function, she says.
She describes her work as a small but important part of a bigger picture.
- This is one piece of a large puzzle, says Golnarnik. - But every piece brings us closer to helping patients.
