Oxidative stress is known to regulate various cellular and biological reactions through oxidative modification of biomolecules by reactive oxygen species (ROS). Oxidative stress itself is known to cause various disease such as cancer, but it has also been reported to play an important role in maintaining biological functions. It is believed that the function of oxidative stress in cells is regulated by the location and concentration of the reaction initiation site, but the details of this regulation have not been clear.
BhcTBHP is a caged compound that can induce oxidative stress responses upon light irradiation. BhcTBHP can release peroxide TBHP, an oxidative stress inducer, upon light irradiation. As shown in Figure 1a, which was evaluated with a peroxide-detecting dye, BhcTBHP quantitatively released TBHP after only 5 minutes of light irradiation. Next, we imaged with a fluorescent dye that reacts with peroxides to see if peroxides can be generated in living cells in the same way. Figure 2a shows that TBHP is also generated in cells (Fig. 1b).
Figure 1 (a) TBHP release from BhcTBHP developed in this study depending on light exposure time and (b) cell experiments using AcBhcTBHP
In addition, MitoTBHP, which targets mitochondria, the main generation site of ROS and a reaction point for various physiological phenomena, was synthesized and its function was evaluated. Cellular imaging using the mitochondrial membrane potential (MMP) measurement probe JC-1 showed a decrease in MMP (Figure 2a). On the other hand, treatment of cells with similar concentrations of TBHP did not alter MMPs (Figure 2b).
Figure 2 MMP changes induced by caged compounds. (a) MitoTBHP, (b) AcBhcTBHP
In conventional methods using oxidative stress inducers, it has been difficult to select a organelle to be acted upon. By using this strategy of caged compounds, more detailed elucidation of the biological functions involved in oxidative stress will become possible, and it is expected to contribute to the elucidation of pathological conditions as a powerful chemical tool.
The research results were published in "Chemical Communication" published by the Royal Society of Chemistry, UK.
Journal: Chemical Communication
Title of paper: Synthesis and photochemical properties of caged peroxides for photocontrol of cellular oxidative stress
Author： Mieko Tsuji,* Haruno Taira, Taro Udagawa, Tatsuya Aoki, Tasuku Hirayama, Hideko Nagasawa*
DOI number: 10.1039/d3cc01192e
Laboratory HP: Laboratory of Pharmaceutical & Medicinal Chemistry