Oxidative stress can arises when cells are exposed to increased reactive oxygen species (ROS) and/or reactive nitrogen species (RNS). This occurs when there is enhancement of ROS and/or RNS production together with inhibition of their removal by glutathione-dependent peroxidases.  The mitochondria are the most important source of ROS, mainly through autoxidation of ubisemiquinone, which occurs in mitochondrial complex III.  The formation of ROS occurs normally under physiological aerobic condition; however, endogenous GSH-dependent antioxidants maintain the cellular reduce state.   Consequently, depletion of intracellular GSH allows a rapid accumulation of ROS, which can be lethal for normal aerobic cells.  This process can be enhanced by inhibition of mitochondrial electron transport, through loss of cytochrome C, or because of increased electron flow that occurs through the uncoupling action of some drugs.  Non-mitochondrial cellular sources of ROS include CYP2E1, peroxisomal oxidases, iron and copper overload, endogenous catechols, and NADPH oxidase of phagocytic cells.  The biochemical consequences of oxidative stress include lipid peroxidation, lipid hydroperoxide-induce DNA damage, protein thiol oxidation, DNA oxidation, protein oxidation, changes in the GSSG/GSH redox couple, and changes in the mitochondrial coenzyme A (CoA)-SSG/CoASH couple.  Massive oxidative stress, particularly in mitochondria, induces necrosis; whereas somewhat lesser exposures may be sufficient to trigger apoptosis.  Aside from initiating apoptosis, oxidative stress may occur as a downstream secondary event due to uncoupling of mitochondria, cytochrome c release, or the export of cellular GSH that accompanies apoptosis.  In certain situations, oxidative stress can protect against apoptosis in some circumstances through the ROS-mediated inhibition of caspases by ROS or the increased expression of survival genes.  This symposium will review the effects of oxidative stress on DNA and proteins, and assess its role in allergic asthma.  Supported by NIH grants R01CA158328, P42ES023720, and P30ES013508.

Overview of oxidative stress in toxicology

248th National Meeting (2014)

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