The endoplasmic reticulum generates reactive oxygen species which amounts to nearly 25% of ROS in the cell, a study reports. Prof. Wang Lei and Wang Chih-chen’s team from the Chinese Academy of Sciences’ Institute of Biophysics (IBP), along with Prof. Liu Guanghui’s group from the Institute of Zoology, CAS, conducted the study.
Reactive Oxygen Species (ROS) are chemically reactive molecules that contain oxygen. ROS are the by-products of metabolism. Examples of ROS include superoxide radicals, hydrogen peroxide, and hydroxyl radicals.
When ROS production exceeds the body’s ability to neutralize or detoxify them with antioxidants, it can lead to oxidative stress. Oxidative stress causes damage to cellular components like DNA, proteins, and lipids. This damage has been implicated in various age-related diseases and conditions, including neurodegenerative disorders, cardiovascular diseases, and cancer.
Endoplasmic Reticulum Release ROS
The research conducted highlighted the connection between oxidative protein folding that occurs in the endoplasmic reticulum and the aging of stem cells, making this the first time such a relationship has been studied. The study observed that hydrogen peroxide (H2O2) produced during oxidative protein folding in the endoplasmic reticulum (ER) could be released or get leaked into the nucleus.
Hydrogen peroxide in the nucleus activates the expression of SERPINE1 a crucial factor that encourages cell senescence.
The research findings indicate that in aged human mesenchymal cells and other cell types, there appears to be an accumulation of the protein disulfide isomerase (PDI), an essential oxidoreductase enzyme responsible for facilitating oxidative protein folding.
When the researchers knocked out the gene for PDI, the rate of oxidative protein folding minimized as well as the leakage of hydrogen peroxide to the nucleus decreased significantly further diminishing SERPINE1 levels, a molecule responsible for cell death.
Potential Benefits of the Study
By thoroughly understanding the mechanisms that trigger cellular senescence in cells, future studies could have profound implications for regenerative medicine. By targeting PDI or related pathways, it may be possible to develop interventions that slow down or reverse the aging process in stem cells, making them more effective for regenerative therapies.
Cellular senescence is closely linked to various age-related diseases, such as neurodegenerative disorders, cardiovascular diseases, and arthritis. Results from this study may pave the way for developing novel therapeutic strategies to combat such conditions by affecting PDI or its related pathways.
The study brings our attention to the delicate relationship between oxidative protein folding, ROS (hydrogen peroxide), and cell senescence. This could contribute to a better understanding of redox signaling and the role of oxidative stress in cellular processes, potentially leading to potential advancements in antioxidant therapies.
PDI and related pathways could potentially serve as promising targets for drug development. Discovering compounds that selectively target PDI activity could lead to new therapeutic agents for age-related diseases and conditions associated with cellular senescence.
The identification of SERPINE1’s role in cell senescence and its association with PDI could lead to the development of identifying biomarkers for aging-related diseases. These biomarkers could aid in the early diagnosis and monitoring of age-related conditions.