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'''Redox signaling''' is the concept that ], ] and electrochemically active oxides of nitrogen such as ] act as biological messengers. Examples of reactive oxygen species include ] and ]. 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 ] also mediate redox signaling. 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>. For example, ] likely play a key role in fibrocyte activation<ref>{{cite pmid|16297593}}</ref><ref>{{cite pmid|11134893}}</ref> and thus scar formation. '''Redox signaling''' is the concept that ], ] and electrochemically active oxides of nitrogen such as ] act as biological messengers. Examples of reactive oxygen species include ] and ]. 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 ] also mediate redox signaling. 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> For example, ] likely play a key role in fibrocyte activation<ref>{{cite pmid|16297593}}</ref><ref>{{cite pmid|11134893}}</ref> and thus scar formation.

==History== ==History==
In a series of papers beginning in 1941,<ref>], A., 1941b. The study of energy-levels in In a series of papers beginning in 1941,<ref>], A., 1941b. The study of energy-levels in
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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 ]. 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 "Reactive oxygen species are messengers" component of redox signaling appears to be that of ], who proposed a role for such species in neuromodulation and neuropsychiatric disease.<ref>{{cite pmid|4680784}}</ref><ref>Proctor, P.; McGinness, J.E. (1970). "Levodopa side-effects and the Lesch-Nyhan syndrome". Lancet 2: 1367</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 ]) 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 "]" adenylylated nucleotides as a specific response to oxidative stress in bacteria. Similarly, the first modern statement of the "Reactive oxygen species are messengers" component of redox signaling appears to be that of ], who proposed a role for such species in neuromodulation and neuropsychiatric disease.<ref>{{cite pmid|4680784}}</ref><ref>Proctor, P.; McGinness, J.E. (1970). "Levodopa side-effects and the Lesch-Nyhan syndrome". Lancet 2: 1367</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 ]) 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 "]" adenylylated nucleotides as a specific response to oxidative stress in bacteria.


==Electronic conduction in redox signaling== ==Electronic conduction in redox signaling==

Revision as of 15:50, 5 December 2012

Redox signaling is the concept that free radicals, reactive oxygen species and electrochemically active oxides of nitrogen such as nitric oxide act as biological messengers. Examples of reactive oxygen species include hydrogen peroxide and superoxide radical. Arguably, hydrogen sulfide and carbon monoxide also mediate redox signaling. Similarly, modulation of charge-transfer processes and electronic conduction in macromolecules is also redox signaling. For a review, see Forman. For example, reactive oxygen species likely play a key role in fibrocyte activation and thus scar formation.

History

In a series of papers beginning in 1941, Szent-Gyorgyi proposed that modulation of electronic processes in semiconductive macromolecules plays a key role in biological function and in diseases such as cancer. Hush reviews the history of such molecular electronics.

Similarly, the first modern statement of the "Reactive oxygen species are messengers" component of redox signaling appears to be that of Proctor, who proposed a role for such species in neuromodulation and neuropsychiatric disease. 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. The next reference seems to be Bochner and coworkers., reporting increased synthesis of "alarmome" adenylylated nucleotides as a specific response to oxidative stress in bacteria.

Electronic conduction in redox signaling

Hush credits Mcginness and coworkers . with the first experimental confirmation of Szent-Gyorgyi's theories concerning semiconductor mechanisms in cellular signaling. Priel and coworkers postulate active electrochemical mechanisms in modulation of cellular processes by microtubules. Bettinger and Bao 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 hydrogen peroxide underlies much biotic and abiotic stress signaling. For example, as signaling molecules, hydrogen peroxide and other ROS post- translationally modify target proteins by oxidizing thiol groups, thus forming disulfide bonds that reversibly alter protein structure and function. Specificity is achieved by localized production, concatenate hormone or calcium signaling, with targeted secondary oxidation occurring via glutaredoxins or thioredoxins. Target proteins containing reduction-oxidation (redox) sensitive thiol groups include i) signal transduction pathway proteins, such as phosphatases and mitogen-activated protein kinases, ii) embryogenesis regulating proteins iii) many transcription factors, iv) RNA-binding proteins that direct DNA methylation, and v) proteins involved in histone acetylation, deacetylation or methylation.

Similarly, the tyrosine-specific Protein Tyrosine Phosphatases are intracellular activities lacking disulfide bonds, but they might sense intracellular redox potential through the conserved cysteine in their active sites An intracellular oscillation of oxidant levels has been experimentally linked to maintenance of the rate of cell proliferation.

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.

Thioredoxin (Trx) signaling Is also important in Cancer, as are other aspects of redox signaling.

References

  1. 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.
  2. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19735727, please use {{cite journal}} with |pmid=19735727 instead.
  3. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 16297593, please use {{cite journal}} with |pmid=16297593 instead.
  4. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 11134893, please use {{cite journal}} with |pmid=11134893 instead.
  5. Szent-Gyorgyi, 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.
  6. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 14976006, please use {{cite journal}} with |pmid= 14976006 instead.
  7. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 4680784, please use {{cite journal}} with |pmid=4680784 instead.
  8. Proctor, P.; McGinness, J.E. (1970). "Levodopa side-effects and the Lesch-Nyhan syndrome". Lancet 2: 1367
  9. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 6393156, please use {{cite journal}} with |pmid=6393156 instead.
  10. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 6373012, please use {{cite journal}} with |pmid=6373012 instead.
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  22. "Tyrosine specific protein phosphatases at PROSITE"Template:Inconsistent citations{{cite web}}: CS1 maint: postscript (link)
  23. "Interpro record for Tyrosine specific protein phosphatases"Template:Inconsistent citations{{cite web}}: CS1 maint: postscript (link)
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  26. http://www.mdanderson.org/education-and-research/departments-programs-and-labs/labs/powis-laboratory/current-research/index.html
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Further reading

External links

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