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| '''Redox signaling''' is cellular ], ] (chemically reactive molecules containing oxygen), and other electrochemically active species such as ] acting as biological messengers. Arguably, ]<ref>Jerzy Bełtowski and Anna Jamroz-Wiśniewska, Modulation of H2S Metabolism by Statins: A New Aspect of Cardiovascular Pharmacology . Antioxidants & Redox Signaling. July 1, 2012, 17(1): 81-94. doi:10.1089/ars.2011.4358.</ref> and ] are also redox signaling molecules. Similarly, modulation of charge-transfer processes and electronic conduction in macromolecules is also redox signaling. For a review, see Forman.<ref>{{cite pmid|19735727}}</ref>. Some redox signaling molecules are as simple as ], while others are much more complex chemicals and organic compounds. For example, ] likely play a key role in fibrocyte activation<ref>{{cite pmid|16297593}}</ref><ref>{{cite pmid|11134893}}</ref> and thus scar formation. | |||
| {{R with history}} | |||
| ==History== | |||
| In a series of papers beginning in 1941,<ref>], A., 1941b. The study of energy-levels in | |||
| biochemistry. Nature 148 (3745), 157–159. | |||
| Szent-Gyorgyi, A., 1957. Bioenergetics. Academic Press, New | |||
| York. | |||
| Szent-Gyorgyi, A., 1960. Introduction to a Submolecular Biology. | |||
| Academic Press, New York. | |||
| Szent-Gyorgyi, A., 1968. Bioelectronics. Academic Press, New | |||
| York. | |||
| Szent-Gyorgyi, A., 1976. Electronic Biology and Cancer. Marcel | |||
| Dekker, Inc., New York. | |||
| Szent-Gyorgyi, A., 1978. The Living State and Cancer. Marcel | |||
| Dekker, Inc., New York.</ref> ] proposed that modulation of electronic processes in semiconductive macromolecules plays a key role in biological function and in diseases such as cancer. Hush <ref>{{Cite pmid| 14976006}}</ref> reviews the history of such ]. | |||
| Similarly, the first modern statement of the "ROS are messengers" component of redox signaling appears to be that of ],.<ref>{{cite pmid|4680784}}</ref> At a 1979 congress of free radical investigators he further generalized this concept to suggest that " ....active oxygen metabolites act as specific intermediary transmitter substances for a variety of biological processes including inflammation, fibrosis, and possibly, neurotransmission.." and " One explanation for this data is that various active oxygen species ( or such products as hydroperoxides ) may act as specific transmitter substances....". After initial opposition, this global concept was published in a 1984 review.<ref>{{cite pmid|6393156}}</ref> The next reference seems to be Bochner and coworkers.,<ref>{{cite pmid|6373012}}</ref> reporting increased synthesis of "alarmome" adenylylated nucleotides as a specific response to oxidative stress in bacteria. | |||
| ==Electronic conduction in redox signaling== | |||
| Hush <ref>{{cite pmid| 14976006}}</ref> credits ] and coworkers .<ref>{{cite pmid|4359339}}</ref> with the first experimental confirmation of Szent-Gyorgyi's theories concerning semiconductor mechanisms in cellular signaling. Priel and coworkers <ref>{{cite pmid|16565058}}</ref> postulate active electrochemical mechanisms in modulation of cellular processes by microtubules. Bettinger and Bao <ref>{{cite pmid|20607127}}</ref> review recent work on biomaterial-based organic electronic devices. Such may play a role in control of cellular function. | |||
| ==Reactive oxygen species as messengers== | |||
| The formation of ROS such as ]<ref>{{Cite pmid| 20446770}}</ref> underlies much biotic and abiotic stress signaling. For example, as signaling molecules, hydrogen peroxide and other ROS post- translationally modify target proteins by oxidizing ] ], thus forming ] that reversibly alter protein structure and function. Specificity is achieved by localized production, concatenate ] or ], with targeted secondary oxidation occurring via ]s or ]s.<ref>{{Cite pmid|18544350}}</ref> Target proteins containing reduction-oxidation (redox) sensitive thiol groups include i) signal transduction pathway proteins, such as ]s<ref>{{Cite pmid| 20919935}}</ref> and ]s,<ref>{{cite pmid| 10717008}}</ref> ii) embryogenesis regulating proteins<ref>{{Cite pmid| 20367257}}</ref> iii) many ]s, iv) ]s that direct ], and v) proteins involved in ] ], deacetylation or ].<ref>{{Cite pmid| 20609913}}</ref><ref>{{cite pmid|20446770}}</ref> | |||
| Similarly, the tyrosine-specific ] are intracellular activities lacking disulfide bonds, but they might sense intracellular redox potential through the conserved cysteine in their active sites <ref>{{Cite web |title=Tyrosine specific protein phosphatases at PROSITE |url=http://www.expasy.org/prosite/PDOC00323 |postscript=<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}</ref><ref>{{Cite web |title=Interpro record for Tyrosine specific protein phosphatases |url=http://www.ebi.ac.uk/interpro/DisplayIproEntry?ac=IPR017867 |postscript=<!-- Bot inserted parameter. Either remove it; or change its value to "." for the cite to end in a ".", as necessary. -->{{inconsistent citations}}}}</ref> | |||
| An intracellular oscillation of oxidant levels has been experimentally linked to maintenance of the rate of cell proliferation.<ref>{{cite pmid|9054359}}</ref> | |||
| As an example, when chelating redox-active iron is present in the endosomal/lysosomal compartment of cultured epithelial cell line HeLa with the iron chelator desferrioxamine, cell proliferation is inhibited.<ref>{{cite pmid|14583336}}</ref> | |||
| ] (Trx) signaling Is also important in Cancer,<ref>http://www.mdanderson.org/education-and-research/departments-programs-and-labs/labs/powis-laboratory/current-research/index.html</ref> as are other aspects of redox signaling.<ref>{{cite pmid| 22117137}}</ref><ref>{{cite pmid| 22033009}}</ref> | |||
| ==References== | |||
| {{Reflist}} | |||
| ==Further reading== | |||
| *{{cite book |first=Peter H. |last=Proctor |chapter=Free Radicals and Human Disease |title=CRC Handbook of Free Radicals and Antioxidants |year=1989 |volume=1 |pages=209–221 |url=http://www.doctorproctor.com/crcpap2.htm}} | |||
| ==External links== | |||
| *http://www.redoxsignaling.com | |||
| ] | |||
| ] | |||
| ] | |||
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