Reactive oxygen species activate transcription factors

Maziere, C., Ahmardani, G., Dantin, F., Dubois, F, Conte, M.A., and Maziere, J.C., 1999, Oxidized LDL activates STATl and STAT3 transcription factors possible involvement of reactive oxygen species, FEES Lett. 448 49-52... 

It is possible to measure the formation of various radicals such as reactive oxygen species in cells. Reactive oxygen species (ROS) activate the nuclear factor of activated T cell transcription factor (NFAT), which is associated with its dephosphorylation, nuclear translocation, and increased affinity for DNA binding. Vanadium activation of nuclear factor of activated T cells (NFAT) was found to correlate with formation of the ROS H202 and was dependent upon the activity of calcium channels [39], In activated human neutrophiles, vanadium(II), (III), and (IV) increased hydroxyl radical formation and attenuation of myeloperoxidase activity, whereas V(V) did not show these effects. Similar results were seen in a cell-free system [40], Increased lipid peroxidation in liver but not in kidneys was found in normal rats treated with vanadate [41]. 

Mitochondrial oxidative stress and mitochondrial GSH defense affects transcription factor activation. Oxidant stress in mitochondria not only can promote the loss of mitochondrial GSH and mitochondrial functions, but also can promote extramito-chondrial activation of NF-kB and therefore may affect nuclear gene expression. Mitochondria are targets of cytokines leading to the overproduction of reactive oxygen species induced by ceramide, a lipid intermediate of cytokine action and closely associated with apoptosis. Chronic ethanol intake depletes liver mitochondrial glutathione due to an ethanol-induced defect in the transport of GSH from cytosol into the mitochondrial matirix. This sensitizes liver cells to the prooxidant effects of cytokines and prooxidants generated by the oxidative metabolism of ethanol. 

Ravati A, Ahlemeyer B, Becker A, Klumpp S, Krieglstein J (2001) Preconditioning-induced neuroprotection is mediated by reactive oxygen species and activation of the transcription factor nuclear factor-kappaB. J Neurochem 78 909-919 Ray A, Prefontaine KE (1994) Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Proc Natl Acad Sci USA 91 752-756... 

Schreck, R., Richer, P, and Bauerle, P.A., Reactive oxygen species intermediates as apparently widely used messengers in the activation of NFkB transcription factor and HIV, EMBO J., 10, 2247, 1999. 

Besides the physiological relevance of reactive oxygen species (ROS) in regulating the intracellular signalling and activating the transcription factors encoded during the synthesis of pro-inflammatory molecules e.g. cytokines and leukotrienes, oxidative stress further lowers the intracellular thiol and GSH levels related to the activated metabolism of SAA. 

Ma, Q., Battelli, L., and Hubbs, A. F. (2006) Multiorgan autoimmune inflammation, enhanced lymphoproliferation, and impaired homeostasis of reactive oxygen species in mice lacking the antioxidant-activated transcription factor Nrf2. Am. J. Pathol. 168, 1960-1974. 

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