Exposure to harsh conditions, cellular damage, and other factors can cause stress on cells. Stress attributed directly and indirectly to oxygen is referred to as oxidative stress, which is imposed on cells as a result of increased oxidant generation, decreased antioxidant protection, or failure to repair oxidative damage induced by reactive oxygen species (ROS). Multiple pathways contribute to cellular ROS production, including the mitochondrial electron transport chain (ETC), inflammatory signaling, and endoplasmic reticulum (ER) stress. Excessive ROS can activate stress-activated signaling cascades or induce alteration of macromolecules, such as membrane lipids, DNA, and essential proteins, including mitochondrial proteins. Cell stress activates stress response pathways such as the heat shock response and ubiquitin system, which act to maintain proper protein structure and degrade misfolded proteins that could be further damaging to the cell. Cells also use antioxidant molecules in response to oxidative stress; antioxidants inhibit oxidation reactions that can generate ROS and can remove free radical intermediates.
Nitric oxide (NO), a reactive free radical generated from arginine by nitric oxide synthases (NOS), is an important signaling molecule for both intracellular and extracellular messaging. NO affects neuronal transmission, cyclic GMP (cGMP) signaling, and has antimicrobial, inflammatory, and cytotoxic effects. NO can interact with superoxide to produce reactive nitrogen species (RNS) that can cause alterations in macromolecules and work with ROS to cause cell damage.
Both nitric oxide and ROS (oxidative stress) have been implicated in disease states, such as hypertension, stroke, neurodegenerative diseases, and cancer. As such, translation of basic understanding of nitric oxide and cell stress into therapeutic treatments for human disease is an important area of research. We understand in translational research it is essential to ensure that your target is the right target. We offer a variety of bioactive small molecules, including mitochondrial inhibitors, antioxidants, and NOS regulators, for target identification and validation in nitric oxide and cell stress research; a selection of these research tools is shown below.