Oxidative stress
[22] The effects of oxidative stress depend upon the size of these changes, with a cell being able to overcome small perturbations and regain its original state.
[25] DNA damage induced by ionizing radiation is similar to oxidative stress, and these lesions have been implicated in aging and cancer.
[30][31][32] Similar attacks on arachidonic acid produce a far larger set of products including various isoprostanes, hydroperoxy- and hydroxy- eicosatetraenoates, and 4-hydroxyalkenals.
[32][30] In addition to serving as markers, the linoleic and arachidonic acid products can contribute to tissue and/or DNA damage but also act as signals to stimulate pathways which function to combat oxidative stress.
E. coli mutants that lack an active electron transport chain produce as much hydrogen peroxide as wild-type cells, indicating that other enzymes contribute the bulk of oxidants in these organisms.
[42] One possibility is that multiple redox-active flavoproteins all contribute a small portion to the overall production of oxidants under normal conditions.
[citation needed] The best studied cellular antioxidants are the enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase.
Other enzymes that have antioxidant properties (though this is not their primary role) include paraoxonase, glutathione-S transferases, and aldehyde dehydrogenases.
Oxidative stress also plays a role in the ischemic cascade due to oxygen reperfusion injury following hypoxia.
The reactive species produced in oxidative stress can cause direct damage to the DNA and are therefore mutagenic, and it may also suppress apoptosis and promote proliferation, invasiveness and metastasis.
[4] Infection by Helicobacter pylori which increases the production of reactive oxygen and nitrogen species in human stomach is also thought to be important in the development of gastric cancer.
[56] In neuronal progenitor cells, DNA damage is associated with increased secretion of amyloid beta proteins Aβ40 and Aβ42.
[56] AD is associated with an accumulation of DNA damage (double-strand breaks) in vulnerable neuronal and glial cell populations from early stages onward,[57] and DNA double-strand breaks are increased in the hippocampus of AD brains compared to non-AD control brains.
[64][65] Since dietary sources contain a wider range of carotenoids and vitamin E tocopherols and tocotrienols from whole foods, ex post facto epidemiological studies can have differing conclusions than artificial experiments using isolated compounds.
While there is good evidence to support this idea in model organisms such as Drosophila melanogaster and Caenorhabditis elegans,[67][68] recent evidence from Michael Ristow's laboratory suggests that oxidative stress may also promote life expectancy of Caenorhabditis elegans by inducing a secondary response to initially increased levels of reactive oxygen species.
[70][71][72] Recent epidemiological findings support the process of mitohormesis, but a 2007 meta-analysis finds that in studies with a low risk of bias (randomization, blinding, follow-up), some popular antioxidant supplements (vitamin A, beta carotene, and vitamin E) may increase mortality risk (although studies more prone to bias reported the reverse).
[83] Numerous studies have shown that the level of 8-oxo-2'-deoxyguanosine, a product of oxidative stress, increases with age in the brain and muscle DNA of the mouse, rat, gerbil and human.
However, it was recently shown that the fluoroquinolone antibiotic Enoxacin can diminish aging signals and promote lifespan extension in nematodes C. elegans by inducing oxidative stress.
The rise of oxygen levels due to cyanobacterial photosynthesis in ancient microenvironments was probably highly toxic to the surrounding biota.
Under these conditions, the selective pressure of oxidative stress is thought to have driven the evolutionary transformation of an archaeal lineage into the first eukaryotes.
Selective pressure for efficient repair of oxidative DNA damages may have promoted the evolution of eukaryotic sex involving such features as cell-cell fusions, cytoskeleton-mediated chromosome movements and emergence of the nuclear membrane.
[86] Thus, the evolution of meiotic sex and eukaryogenesis may have been inseparable processes that evolved in large part to facilitate repair of oxidative DNA damages.
