Thesis Proposal
Name:Melissa Ruvimbo Chimedza
Student ID :2620150008
Title:Design, Synthesis and Application of Novel Reactive Oxygen Fluorescent Probes
- The background of the project
Reactive oxygen species (ROS), reactive nitrogen species (RNS) and reactive sulfur species (RSS) play important roles in maintaining the redox state in the body. Abnormal changes in the concentration levels and distribution of these species will cause many diseases to occur. Therefore, sensitive visual analysis of these biologically important substances is critical to revealing their detailed biological functions and toxicology. Oxidative stress, an imbalance of reactive oxygen species (ROS) production and antioxidant defenses, is a fundamental process that operates in a diverse array of human diseases, including Alzheimer Qs diseases, cardiovascular disorders, and cancer [1-4].
In the natural environment or in the living body, there are some oxygen-containing substances with strong oxidizing ability and active nature. They are called reactive oxygen species (ROS). Active oxygen can be mainly divided into four categories: (1) singlet oxygen molecules (1O2); (2) three oxygenated free radicals, namely superoxide anion radicals (О2bull;ˉ), hydroxyl radicals (bull;OH) and Hydroperoxide radical (HO2bull;); (3) two kinds of peroxides, namely, ammonia peroxide (H2O2) and lipid peroxide (ROOH); (4) nitrogen oxides (NO) and hypochlorite (ClO-) et al [5,6].
In cells, H2O2 is formed from short lived О2bull;ˉ, which in turn is produced mainly by seven identified sites in mitochondria [7] or by NADPH oxidases (Nox) [8,9]. Previously, it was suggested that NADPH oxidases only exist in immune phagocytic cells, which use superoxide to oxidize molecules of pathogens [10]. However, it turns out that this type of proteins is also present in many types of nonphagocytic cells [11]. Various growth factors, cytokines, and intracellular proteins are involved in the regulation of NADPH oxidase activity [11,12,13], demonstrating once again that the role of superoxide and H2O2 in cellular function is much more diverse than previously thought. In addition, a wide range of other enzymes also participate in the formation of intracellular О2bull;ˉ, mainly as byproducts of their reactions [14,15]. Generated О2bull;ˉ is rapidly converted into H2O2 spontaneously or mostly by the action of specialized enzymes called superoxide dismutases. These enzymes are involved in antioxidant protection in almost all cells. Eukaryotic cells are characterized by the presence of two different superoxide dismutase isoforms localized in the cytosol and mitochondrial matrix [16,17,18], where they restrict the intracellular lifetime of О2bull;ˉ and thereby prevent damage to proteins containing iron-sulfur clusters. In addition, superoxide dismutases catalyze H2O2 formation, which can regulate signaling cascades. The process of production is shown in Figure 1.
Figure 1. Process of reactive oxygen species production
Hydrogen peroxide, as an important member of living oxygen in the body, plays an important role in physiological and pathological systems. Hydrogen peroxide has been known as a by-product of aerobic and phagocytic respiration, but in recent years more and more data have shown that it acts as a second messenger to regulate basic life activities such as wound repair, antibacterial, and stem cells. Hyperplasia and so on. However, abnormal cells produce excessive amounts of hydrogen peroxide, which can cause toxic effects on cells and surrounding tissues. For example, the body will cause oxidative stress damage, and this oxidative damage will accumulate and eventually cause diseased organs to fail [19,20]. Hydrogen peroxide in cells is also closely related to some human diseases, such as malignant tumors, cardiovascular, dysfunction, diabetes and neurodegenerative diseases [21]. It can be seen that the timely and accurate detection of the content of hydrogen peroxide in the body has important guiding significance for the prevention, diagnosis and pathology of certain diseases.
