Consequences of Oxidant Stress

While many biological molecules may be targets for oxidant stress and free radicals, it is clear that the cell membrane and its associated proteins may be particularly vulnerable. The ability of the cell to control its intracellular ionic environment as well as its ability to maintain a polarized membrane potential and electrical excitability depends on the activity of ion-translocating proteins such as channels, pumps and exchangers. Either direct or indirect disturbances of the activity of these ion translocators must ultimately underlie reperfiision and oxidant stress-induced arrhythmias in the heart. A number of studies have therefore investigated the effects of free radicals and oxidant stress on cellular electrophysiology and the activity of key membrane-bound ion translocating proteins. 

2 Oxidant Stress-induced Alterations in Myocardial Glutathione Status 

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A major consequence of oxidative stress is damage to cellular macromolecules. Addition of a free radical... 

C35. Cornu-Labat, G., Serra, M., Smith, A., McGregor, W. E., Kasirajan, K., Hirko, M. K., Turner, J. J., and Rubin, J. R., Systemic consequences of oxidative stress following aortic surgery correlate with the degree of antioxidant defenses. Ann. Vase. Surg. 14, 31—36 (2000). 

Protein thiols can interact with glutathione by several mechanisms that permit glu-tathionylation to participate in the regulation and antioxidant protection of specific protein thiols. These reactions are involved in the consequences of oxidative stress caused by reactive species of oxygen and nitrogen and include the formation of protein sulfenic acids and their participation in regulatory processes. 

The first metastable molecules which accumulate as a consequence of oxidative stress are hydroperoxides. Hydroperoxide-producing enzymes will also result in oxidative stress if they are stimulated over a prolonged period of time. 

Ohia, S.E., Opere, C.A., and Leday, A.M. (2005). Pharmacological consequences of oxidative stress in ocular tissues. Mutat Res 579, 22-36. 

Neurons operate under unique redox conditions, increasing their vulnerability to oxidative stress, and recent studies provide evidence of oxidative stress and neuroinflammation in autism. Impaired methylation is a consequence of oxidative stress, mediated in major part by inhibition of the folate- and cobalamin-dependent enzyme methionine synthase. Since methionine synthase activity is essential for dopamine-stimulated phospholipid methylation, some symptoms of autism may reflect impairment of this process. For example, dopamine D4 receptor activation... 

Possible consequences of oxidative stress in the central nervous system... 

R.P. Mason, Free radical metabolites of toxic chemicals and drugs as sources of oxidative stress, in Biological Consequences of Oxidative Stress. Implications for Cardiovascular Disease and Carcinogenesis, L. Spatz and A.D. Bloom (eds.), Oxford University Press, New York, 1992, p. 23. 

Bochner BR, Lee PC, Wilson SW, Cutler CW, Ames BN (1984) AppppA and related adenylated nucleotides are synthesized as a consequence of oxidation stress. Cell 37 225-232... 

Spatz, L. Introduction, In Biological consequences of oxidative stress Spatz, L. Bloom, A eds., Oxford University Press, New York, NY, 1992 pp3-22. 

A potential consequence of oxidant stress during hypoxia due to alterations in the ROS/NO balance is local formation of lipid inflammatory mediators, such as platelet activating factor and leukotriene These mediators promote leukocyte and platelet adhesiveness to venular endothelium and may contribute to enhanced thrombosis reported during hypoxia. " ... 

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