Redox signaling
Redox signaling is when free radicals, reactive oxygen species (ROS), and other electronically activated species such as nitric oxide and othe oxides of nitrogen 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.[1]
History
The concept of electronically activated species as biological messengers goes back to the 19th century. For example, scientists now know that reactive oxygen species likely play a key role in fibrocyte activation[2] and thus scar formation.
In a series of papers beginning in 1941,[3] 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 [4] 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,[5] who at a congress of free radical investigators in 1979 generalized the 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....". This was formally published in a review in 1984.[6] The next reference seems to be Bochner and coworkers.[7]
Electronic conduction in redox signaling
Hush [8] credits Mcginness and coworkers [9] with the first experimental confirmation of Szent-Gyorgyi's theories concerning semiconductor mechanisms in cellular signaling. Priel and coworkers [10] postulate active electronic mechanisms in modulation of cellular processes by microtubules. Bettinger and Bao [11] review recent work on biomaterial-based organic electronic devices. Such may play s role in control of cellular function.
Reactive oxygen species as messengers
The formation of ROS such as hydrogen peroxide[12] 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.[13] Target proteins containing reduction-oxidation (redox) sensitive thiol groups include i) signal transduction pathway proteins, such as phosphatases[14] and mitogen-activated protein kinases,[15] ii) embryogenesis regulating proteins[16] iii) many transcription factors, iv) RNA-binding proteins that direct DNA methylation, and v) proteins involved in histone acetylation, deacetylation or methylation.[17][18]
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 [19][20] An intracellular oscillation of oxidant levels has been previously experimentally linked to maintenance of the rate of cell proliferation.[21]
As an example, when chelating redox-active iron present in the endosomal/lysosomal compartment of cultured epithelial cell line HeLa with the iron chelator desferrioxamine, cell proliferation is inhibited.[22]
Thioredoxin (Trx) signaling Is also important in Cancer [1], as are other aspects of redox signaling [23]. [24].
References
- ^ Forman, H.J., Signal transduction and reactive species. Free Radic. Biol. Med. 47:1237-1238; 2009.
- ^ . PMID 16297593.
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(help) - ^ 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.
- ^ Hush, N.S. An Overview of the First Half-Century of Molecular Electronics. Ann. N.Y. Acad. Sci. 1006:1–20; 2003.
- ^ Proctor P (1972). "Electron-transfer factors in psychosis and dyskinesia". Physiol. Chem. Phys. 4 (4): 349–60. PMID 4680784.
- ^ http://www.drproctor.com/rev/84/84rev.htm
- ^ Bochner BR, Lee PC, Wilson SW, Cutler CW, Ames BN, (1984). "AppppA and related adenylylated nucleotides are synthesized as a consequence of oxidation stress". Cell. 37 (1): 225–32. doi:10.1016/0092-8674(84)90318-0. PMID 6373012.
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ignored (help)CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link) - ^ Hush, N.S. An Overview of the First Half-Century of Molecular Electronics. Ann. N.Y. Acad. Sci. 1006:1–20; 2003.
- ^ | doi = 10.1126/science.183.4127.853 | volume = 183 | issue = 4127 | pages = 853–855 | title = Amorphous Semiconductor Switching in Melanins | journal = Science | date = 1974-03-01 | last1 = McGinness | first1 = J. | last2 = Corry | first2 = P. | last3 = Proctor | first3 = P. | pmid=4359339}}
- ^ Priel A, Ramos AJ, Tuszynski JA, Cantiello HF. A biopolymer transistor: electrical amplification by microtubules. Biophys J. 2006 Jun 15;90(12):4639-43. Epub 2006 Mar 24. PMID 16565058; PMC 1471843.
- ^ Bettinger CJ, Bao Z. Biomaterials-Based Organic Electronic Devices. Polym Int. 2010 May 1;59(5):563-567. PMID 20607127; PMC 2895275
- ^ Shlomai 2010. Redox Control of Protein-DNA Ineractions: From Molecular Mechanisms to Significance in Signal Transduction, Gene Expresssion, and DNA Replication. Antioxidants and Redox Signaling 13:1429-1476
- ^ Winterbourn C.C., and Hampton M.B. 2008. Thiol chemistry and specificity in redox signaling. Free Radical Biology and Medicine 45: 549-561
- ^ Tanner J.J., Parsons Z.D., Cummings A.H., Zhou H., Gates K.S. 2011. Redox Regulation of Protein Tyrosine Phosphatases: Structural and Chemical Aspects. Antioxidants & Redox Signaling 15:77-97.
- ^ Kovtun Y., Chiu W.L., Tena G., and Sheen J. 2000. Functional analysis of oxidative stress-activated mitogen-activated protein kinase cascade in plants. PNAS 97:2940-2945
- ^ Ufer C, Wang CC, Borchert A, Heydeck D, Kuhn H. 2010. Redox control in mammalian embryo development. Antioxidants & Redox Signaling 13: 833-875
- ^ Sundar IK, Caito S, Yao H, and Rahman I. 2010. Oxidative stress, thiol redox signaling methods in epigenetics. Methods Enzymol.474:213-44.
- ^ Shlomai 2010. Redox Control of Protein-DNA Ineractions: From Molecular Mechanisms to Significance in Signal Transduction, Gene Expresssion, and DNA Replication. Antioxidants and Redox Signaling 13:1429-1476
- ^ Tyrosine specific protein phosphatases at PROSITE
- ^ Interpro record for Tyrosine specific protein phosphatases
- ^ Irani K, Xia Y, Zweier JL; et al. (1997). "Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts". Science. 275 (5306): 1649–52. doi:10.1126/science.275.5306.1649. PMID 9054359.
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ignored (help)CS1 maint: multiple names: authors list (link) - ^ Doulias PT, Christoforidis S, Brunk UT, Galaris D (2003). "Endosomal and lysosomal effects of desferrioxamine: protection of [[HeLa]] cells from hydrogen peroxide-induced DNA damage and induction of cell-cycle arrest". Free Radic. Biol. Med. 35 (7): 719–28. doi:10.1016/S0891-5849(03)00396-4. PMID 14583336.
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ignored (help)CS1 maint: multiple names: authors list (link). - ^ Gupta SC, Hevia D, Patchva S, Park B, Koh W, Aggarwal BB., Upsides and Downsides of Reactive Oxygen Species for Cancer: The Roles of Reactive Oxygen Species in Tumorigenesis, Prevention, and Therapy. Antioxid Redox Signal. 2012 Jan 16. http://www.ncbi.nlm.nih.gov/pubmed/22117137
- ^ Díaz B, Courtneidge SA. Redox signaling at invasive microdomains in cancer cells. Free Radic Biol Med. 2012 Jan 15;52(2):247-56. http://www.ncbi.nlm.nih.gov/pubmed/22033009
Further reading
- Proctor, Peter H. (1989). "Free Radicals and Human Disease". CRC Handbook of Free Radicals and Antioxidants. Vol. 1. pp. 209–221.