Reactive oxygen species



Reactive oxygen species (ROS) include electrons. ROSs form as a natural byproduct of the normal metabolism of oxidative stress.

Damaging effects

Cells are normally able to defend themselves against ROS damage through the use of uric acid.

The effects of ROS on cell metabolism have been well documented in a variety of species. These include not only roles in programmed cell death and platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury. These also provide a link to the adaptive immune system via the recruitment of leukocytes.

Reactive oxygen species are implicated in cellular activity to a variety of inflammatory responses including cardiovascular disease. They may also be involved in hearing impairment via cochlear damage induced by elevated sound levels, ototoxicity of drugs such as apoptosis or programmed cell death and ischaemic injury. Specific examples include stroke and heart attack.

Generally, harmful effects of reactive oxygen species on the cell are most often:

  1. damage of DNA
  2. oxidations of polydesaturated fatty acids in lipids
  3. oxidations of amino acids in proteins
  4. Oxidatively inactivate specific enzymes by oxidation of co-factors

Internal production

Free radicals are also produced inside (and also released towards the cytosol [1][2]) organelles, such as the apoptosis or programmed cell death.

Bcl-2 proteins are layered on the surface of the mitochondria, detect damage, and activate a class of proteins called Bax, which punch holes in the mitochondrial membrane, causing cytochrome C to leak out. This cytochrome C binds to Apaf-1, or apoptotic protease activating factor-1, which is free-floating in the cell’s cytoplasm. Using energy from the ATPs in the mitochondrion, the Apaf-1 and cytochrome C bind together to form apoptosomes. The apoptosomes binds to and activates caspase-9, another free-floating protein. The caspase-9 then cleaves the proteins of the mitochondrial membrane, causing it to break down and start a chain reaction of protein denaturation and eventually phagocytosis of the cell.

Cause of aging

According to the Free-radical theory, oxidative damage intiated by reactive oxygen species is a major contributor to the functional decline that is characteristic of aging. While studies in invertebrate models indicate that animals genetically engineered to lack specific antioxidant enzymes (such as SOD) generally show a shortned lifespan (as one would expect from the theory), the converse, increasing the levels of antioxidant enzymes, has yielded inconsistent effects on lifespan (though some well-performed studies in Drosophila do show that lifespan can be increased by the overexpression of MnSOD or glutathione biosynthesizing enzymes). In mice, the story is somewhat similar. Deleting antioxidant enzymes generally yields shorter lifespan, though overexpression studies have not (with some recent exceptions), consistenly extended lifespan [3].

Superoxide dismutase

Fenton chemistry), one of the most destructive free radicals. Catalase, which is concentrated in peroxisomes located next to mitochondria but formed in the rough endoplasmic reticulum and located everywhere in the cell, reacts with the hydrogen peroxide and forms water and oxygen. Glutathione peroxidase reduces hydrogen peroxide by transferring the energy of the reactive peroxides to a very small sulfur containing protein called glutathione. The selenium contained in these enzymes acts as the reactive center, carrying reactive electrons from the peroxide to the glutathione. Peroxiredoxins also degrade H2O2, both within the mitochondria, cytosol and nucleus.

See also

References

  • Sen, C.K. (2003) The general case for redox control of wound repair, Wound Repair and Regeneration, 11, 431-438
  • Krötz, F., Sohn, HY., Gloe, T., Zahler, S., Riexinger, T., Schiele, T.M., Becker, B.F., Theisen, K., Klauss, V., Pohl, U. (2002) NAD(P)H oxidase-dependent platelet superoxide anion release increases platelet recruitment, Blood, 100, 917-924
  • Pignatelli, P. Pulcinelli, F.M., Lenti, L., Gazzaniga, P.P., Violi, F. (1998) Hydrogen Peroxide Is Involved in Collagen-Induced Platelet Activation, Blood, 91 (2), 484-490
  • Guzik, T.J., Korbut, R., Adamek-Guzik, T. (2003) Nitric oxide and superoxide in inflammation and immune regulation, Journal of Physiology and Pharmacology, 54 (4), 469-487
  • Free Radicals and Human Disease, a Review
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Reactive_oxygen_species". A list of authors is available in Wikipedia.