Oxidative stress

The 2013 U.S. Surgeon General’s Report “How Tobacco Smoke Causes Diseases” identifies oxidative stress as one of the key mechanisms underlying all major smoking-related diseases1.

Oxidative stress results from imbalance between the levels of reactive oxygen species (ROS) and antioxidants. ROS and other reactive species act directly on cellular macromolecules damaging lipids, proteins and DNA.

Multiple lines of evidence suggest that ROS are key contributors to molecular signaling pathways underlying the development of atherosclerosis2,3 and play a central role in modifying most of the known main risk factors for CVD including hypertension, hypercholesterolemia, obesity, and diabetes4-7.

Key players of the oxidative stress response include the transcription factors AP-1, NF-KB and Nrf28.

In general, cells respond to oxidative stress by activation of the transcription factor Nrf-2 (encoded by the NFE2L2 gene), a key regulator of detoxification and antioxidant genes9. When expressed, the products of these genes then either act as quenchers to eliminate the oxidative insult or contribute to the regulation of downstream effectors that determine cell fate based on the extent of damage.

However, oxidative damage is also known to elicit a number of other cellular responses triggering various protein kinase signaling cascades, most notably those of the mitogen-activated protein kinase (MAPK) family, and resulting in proliferation, growth arrest, senescence or cell death, typically depending on the type of stressor and the duration and extent of stress10.

References

  1. Services, U.D.o.H.a.H., How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease: a report of the Surgeon General. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2010. 2.
  2. Madamanchi, N.R., A. Vendrov, and M.S. Runge, Oxidative Stress and Vascular Disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 2005. 25(1): 29-38.
  3. Harrison, D., et al., Role of oxidative stress in atherosclerosis. The American journal of cardiology, 2003. 91(3): 7-11.
  4. Ceriello, A. and E. Motz, Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arteriosclerosis, Thrombosis, and Vascular Biology, 2004. 24(5): 816-823.
  5. Keaney, J.F., et al., Obesity and systemic oxidative stress clinical correlates of oxidative stress in the Framingham Study. Arteriosclerosis, Thrombosis, and Vascular Biology, 2003. 23(3): 434-439.
  6. Rodriguez-Porcel, M., et al., Hypercholesterolemia impairs myocardial perfusion and permeability: role of oxidative stress and endogenous scavenging activity. Journal of the American College of Cardiology, 2001. 37(2): 608-615.
  7. Asmat, U., K. Abad, and K. Ismail, Diabetes mellitus and oxidative stress—A concise review. Saudi Pharmaceutical Journal, 2015.
  8. Schlage, W., et al., A computable cellular stress network model for non-diseased pulmonary and cardiovascular tissue. BMC Systems Biology, 2011. 5(1): 168.
  9. Ishii, T., K. Itoh, and M. Yamamoto, Roles of Nrf2 in activation of antioxidant enzyme genes via antioxidant responsive elements. Methods in Enzymology, 2002. 348: 182-190.
  10. Martindale, J.L. and N.J. Holbrook, Cellular response to oxidative stress: Signaling for suicide and survival. Journal of Cellular Physiology, 2002. 192(1): 1-15.

Oxidative stress Results

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