Apoptosis reactive oxygen species

Anthracyclins. Figure 2 Mechanisms of anthracycline-induced apoptosis of tumor cells. ROS, reactive oxygen species topo II, topoisomerase II cyt c, cytochrome c. 

InSug O, Datar S, Koch CJ, Shapho IM, Shenker BJ. 1997. Mercuric compounds inhibit human monocyte function by inducing apoptosis evidence for formation of reactive oxygen species, development of mitochondrial membrane permeabflity transition and loss of reductive reserve. Toxicology 124 211-224. 

Paik SY, Koh KH, Beak SM, Paek SH, Kim JA. The essential oils from Zanthoxylum schinifolium pericarp induce apoptosis of HepG2 human hepatoma cells through increased production of reactive oxygen species. Biol Pharm Bull 2005 28 802-807. 

Cui, Y., Lu, Z., Bai, L., Shi, Z., Zhao, W.E., and Zhao, B. 2007. Beta-carotene induces apoptosis and up-regulates peroxisome proliferator-activated receptor gamma expression and reactive oxygen species production in MCF-7 cancer cells. EurJ Cancer 43 2590-2601. 

Mechanisms of the Activation of Apoptosis by Reactive Oxygen Species... 

Colquhoun and Schumacher [98] have shown that y-linolcnic acid and eicosapentaenoic acid, which inhibit Walker tumor growth in vivo, decreased proliferation and apoptotic index in these cells. Development of apoptosis was characterized by the enhancement of the formation of reactive oxygen species and products of lipid peroxidation and was accompanied by a decrease in the activities of mitochondrial complexes I, III, and IV, and the release of cytochrome c and caspase 3-like activation of DNA fragmentation. Earlier, a similar apoptotic mechanism of antitumor activity has been shown for the flavonoid quercetin [99], Kamp et al. [100] suggested that the asbestos-induced apoptosis in alveolar epithelial cells was mediated by iron-derived oxygen species, although authors did not hypothesize about the nature of these species (hydroxyl radicals, hydrogen peroxide, or iron complexes ). 

After considering experimental data relevant to the participation of mitochondrial reactive oxygen species in the development of apoptosis, we may now regard mechanisms of the... 

Similar to reactive oxygen species, nitric oxide, peroxynitrite, and other nitrogen oxide species produced by mitochondria are able to stimulate or inhibit apoptosis. Proapoptotic effect of nitric oxide was probably first shown by Albina et al. [138], who demonstrated NO-induced... 

Greenlund, L. J., Deckwerth, T. L. and Johnson, E. M. Jr. Superoxide dismutase delays neuronal apoptosis a role for reactive oxygen species in programmed neuronal death. Neuron 14 303-315,1995. 

Several different changes in mitochondria occur during apoptosis. These include a change in membrane potential (usually depolarization), increased production of reactive oxygen species, potassium channel activation, calcium ion uptake, increased membrane permeability and release of cytochrome c and apoptosis inducing factor (AIF) [25]. Increased permeability of the mitochondrial membranes is a pivotal event in apoptosis and appears to result from the formation of pores in the membrane the proteins that form such permeability transition pores (PTP) may include a voltage-dependent anion channel (VDAC), the adenine nucleotide translocator, cyclophilin D, the peripheral benzodiazepine receptor, hexokinase and... 

Mitochondrial function. NO is able to react with transition metals such as iron, including those contained within haem groups. Even at low NO concentrations there is competition between oxygen and NO for reversible binding to cytochrome c oxidase. If mitochondrial 02 is low respiration slows, which may confer anti-apoptotic benefit to the cell. As NO concentration rises and peroxynitrite is formed, electron transport is irreversibly inhibited, there is increased production of superoxide and other reactive oxygen species and apoptosis occurs. 

Antonsson and Marinou 2000 Adams and Cory, 1998). Stress may also cause inaease, nitric oxide (NO), or reactive oxygen species (ROS) production which, in turn, triggers release of apoptotic proteins from the intermemhrane space (Kroemer and Reed, 2000 Vieira et at, 2000). Release of these proteins from mitochondria are required for stress induced killing hut are, with a few exceptions (Bergmann et al, 1994, Schulze- Osthoff et al, 1993), dispensible for CD95 and TNF-receptor transduced apoptosis. These other death processes require FADD and caspase-8 to be recruited into the death receptor complexes and cannot be blocked by Bcl-2 (Krammer, 2000 Scaffidi et al, 1998). 

Li, P.F., Dietz, R., and von Harsdorf, R., 1999, P53 regulates mitochondrial membrane potential through reactive oxygen species and induces cytochrome c-independent apoptosis blocked by Bcl-2, EMBO J. 18 66027-6036. 

In the literature, most dmg-induced apoptosis is well known to require intracellular hyper-production of reactive oxygen species and several antioxidants inhibit apoptotic cell death. While it is clear that peroxidation reactions induce apoptosis, the precise molecular mechanism of how reactive oxygen species convey death-signals is unknown. 

Hsieh, C.C., Yen, M.H., Yen, C.H., Lau, Y.T., 2001, Oxidized low density hpoprotein induces apoptosis via generation of reactive oxygen species in vascular smooth muscle cells, Cardiovasc. Res. 49 135-145. 

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