oxidative stress
Pathology
Disorders associated with oxidative stress include:
- myocardial ischemia & myocardial infarction
- ischemic stroke
- Alzheimer's disease
- Huntington's disease
- amyotrophic lateral sclerosis
- Parkinson's disease
- Tourette syndrome
- methemoglobinemia
- pyruvate kinase deficiency
- glucose-6-phosphate dehydrogenase deficiency
Biochemistry
Exposure of cells to pro-oxidant conditions (excessive oxidizing potential) & the cellular response to the stress.
The cellular response to oxidative stress is mediated (in part) by genes containing the antioxidant-response element (ARE). The ARE is activated by the transcription factor Nrf2.
Mediators of oxidative stress include:
- superoxide (O2-.),
- hydrogen peroxide (H2O2)
- hydroxyl radical (OH.)
Excessive production of mediators of oxidative stress or diminished protective mechanisms to remove them may result in:
- enhanced inflammatory response with secondary tissue damage
- apoptosis
The biochemistry of oxygen & its partial reduction products (O2-., H2O2 & OH.) is not so simple as to allow for simply mopping up this class of 'bad actors'. H2O2 & O2-. are intermediates in enzymatic reactions essential for normal metabolism, including immunological responses.[3][4] The free radical theory on aging[5] & disease[6] has served as a basis of intensive research on oxidative stress since 1956.
More general terms
Additional terms
References
- ↑ Nguyen T et al, Ann Rev Pharmacol Toxicol 43:233, 2003
- ↑ UpToDate version 11.3 2003 http://www.uptodate.com
- ↑ 3.0 3.1 Ball SS. Weindruch R. Walford RL. Antioxidants and the immune response. In: Free Radicals, Aging and Degenerative Disease. Johnson, J.E. (ed.) Modern Aging Research vol. 8, NY: Alan R. Liss pp 427-456, 1986
- ↑ 4.0 4.1 Nanni E. Sawyer DT. Ball SS. Bruice TC. Redox chemistry of N(5)-ethyl-3-methylflavinium cation and N(5)-ethyl-4a-hydroperoxy-3-methyllumiflavin in dimethyl- formamide; evidence for the formation of the N(5)-ethyl-4a- hydroperoxy-3-methyllumiflavin anion via radical-radical coupling with superoxide ion. J. Am. Chem. Soc. 103:2797, 1981
- ↑ 5.0 5.1 Harman D, Aging: a theory based on free radical and radiation chemistry, J Gerontol 11:298, 1956
- ↑ 6.0 6.1 Harman D, Free radical theory of aging: Role of free radicals in the origination and evolution of life, aging and disease processes. In: Johnson JE et al (eds), Free Radicals, Aging and Degenerative Diseases, New York, Liss, 1986