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'''Redox signaling''' is cellular communication by ], ] (chemically reactive molecules containing oxygen), and other electrochemically active species such as ], which act 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. '''Redox signaling''' is cellular ], ] (chemically reactive molecules containing oxygen), and other electrochemically active species such as ] which act 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.
==History== ==History==

Revision as of 02:39, 27 October 2012

Redox signaling is cellular free radicals, reactive oxygen species (chemically reactive molecules containing oxygen), and other electrochemically active species such as nitric oxide which act as biological messengers. Arguably, hydrogen sulfide and carbon monoxide 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.. Some redox signaling molecules are as simple as hydrogen peroxide, while others are much more complex chemicals and organic compounds. 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 "ROS are messengers" component of redox signaling appears to be that of Proctor,. 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.
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  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.
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  21. "Tyrosine specific protein phosphatases at PROSITE"Template:Inconsistent citations{{cite web}}: CS1 maint: postscript (link)
  22. "Interpro record for Tyrosine specific protein phosphatases"Template:Inconsistent citations{{cite web}}: CS1 maint: postscript (link)
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  25. 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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