Figure 4

Schematic overview of the biological events involved in NADPH oxidase during PMA-induced respiratory burst in differentiated HL-60 cells. PMA activates protein kinase C (PKC), which signals to the nucleus, activating cyclooxygenase (COX) and phospholipase A₂ (PLA2) pathways, leading to the production of prostaglandins. O₂ ^.−is first produced by NADPH oxidase as a primary ROS and is subsequently dismutated to H₂O₂ by superoxide dismutase (SOD). Thus, H₂O₂ serves as a substrate for generating hydroxyl radicals (OH^•) via the Fenton reaction. Hydroxyl radicals (OH^•) are potent oxidants that can produce the initial radical (R•) form of a wide range of biomolecules, including lipids, proteins, and nucleic acids. Via this mechanism, molecular oxygen is added to produce a peroxyl radical (ROO^•), followed by cyclisation to produce dioxetane (ROOR) and decomposition to produce triplet excited carbonyl²³. Alternatively, two ROO^• moieties can recombine to form tetroxide (ROOOOR), which can decompose to form triplet excited carbonyl or singlet oxygen via the Russel reaction²³. These electron-excited species emit photons, giving rise to UPE²³. Eventually, intracellular ROS can react with biomolecules in the cell membrane (i.e. lipid peroxidation), giving rise to isoprostanes. Treating differentiated HL-60 cells with DPI, which binds to the NADPH oxidase complex, partially inhibits ROS production, decreases UPE emission, and decreases the levels of prostaglandins and isoprostanes. This figure was drawn by the first author R.C.R. Burgos using the software Adobe Illustrator and the image bank of Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License. https://creativecommons.org/licenses/by/3.0/.