Reactive Oxygen Species and Alpha,beta-unsaturated Aldehydes As Second Messengers in Signal Transduction

Overview

Journal Ann N Y Acad Sci

Specialty Science

Date 2010 Aug 19

PMID 20716281

Citations 42

Authors

Henry Jay Forman

Affiliations

Soon will be listed here.

Abstract

Signaling by H(2)O(2), alpha,beta-unsaturated aldehydes, such as 4-hydroxy-2-nonenal (HNE) and related chemical species, is thought to differ from signaling by other second messengers because the oxidants and other electrophiles can readily undergo nonenzymatic reactions and are therefore classified as "reactive." This brief review will describe how and when the chemistry of signaling is similar or differs from classic second messengers, such as cyclic AMP, or posttranslational signaling, such as farnesylation or ubiquitination. The chemistry of cysteine provides a common factor that underlies signaling by H(2)O(2) and HNE. Nonetheless, as H(2)O(2) and HNE are rapidly metabolized in vivo, spatial considerations are extremely important in their actions. Therefore, the locations of sources of H(2)O(2) and alpha,beta-unsaturated aldehydes, the NADPH oxidases, mitochondria, membrane lipids, and redox cycling toxicants, as well as their targets, are key factors. The activation of the JNK pathway by HNE and endogenously generated H(2)O(2) illustrates these principles.

Citing Articles

Mechanisms and preventive measures of ALDH2 in ischemia‑reperfusion injury: Ferroptosis as a novel target (Review).

Han L, Zhai W Mol Med Rep. 2025; 31(4).

PMID: 40017132 PMC: 11876945. DOI: 10.3892/mmr.2025.13470.

Predicting Chronological Age via the Skin Volatile Profile.

Finnegan M, Fitzgerald S, Duroux R, Attia J, Markey E, OConnor D J Am Soc Mass Spectrom. 2024; 35(3):421-432.

PMID: 38326105 PMC: 10921460. DOI: 10.1021/jasms.3c00315.

Mitochondrial Dysfunction-Associated Mechanisms in the Development of Chronic Liver Diseases.

Arumugam M, Gopal T, Kalari Kandy R, Boopathy L, Perumal S, Ganesan M Biology (Basel). 2023; 12(10).

PMID: 37887021 PMC: 10604291. DOI: 10.3390/biology12101311.

Aldehyde dehydrogenase 3A1 deficiency leads to mitochondrial dysfunction and impacts salivary gland stem cell phenotype.

Viswanathan V, Cao H, Saiki J, Jiang D, Mattingly A, Nambiar D PNAS Nexus. 2022; 1(2):pgac056.

PMID: 35707206 PMC: 9186046. DOI: 10.1093/pnasnexus/pgac056.

Inhibition Mechanism of L-Cysteine on Maillard Reaction by Trapping 5-Hydroxymethylfurfural.

Yang S, Zhang Z, Li J, Niu Y, Yu L Foods. 2021; 10(6).

PMID: 34208512 PMC: 8234683. DOI: 10.3390/foods10061391.

References

Akerboom T, Sies H . Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol. 1981; 77:373-82. DOI: 10.1016/s0076-6879(81)77050-2. View

Peskin A, Low F, Paton L, Maghzal G, Hampton M, Winterbourn C . The high reactivity of peroxiredoxin 2 with H(2)O(2) is not reflected in its reaction with other oxidants and thiol reagents. J Biol Chem. 2007; 282(16):11885-92. DOI: 10.1074/jbc.M700339200. View

Sutherland M, Nelson J, Harrison G, Forman H . Effects of t-butyl hydroperoxide on NADPH, glutathione, and the respiratory burst of rat alveolar macrophages. Arch Biochem Biophys. 1985; 243(2):325-31. DOI: 10.1016/0003-9861(85)90509-0. View

Cha M, Kim I . Thioredoxin-linked peroxidase from human red blood cell: evidence for the existence of thioredoxin and thioredoxin reductase in human red blood cell. Biochem Biophys Res Commun. 1995; 217(3):900-7. DOI: 10.1006/bbrc.1995.2856. View

Chiarugi P, Fiaschi T, Taddei M, Talini D, Giannoni E, Raugei G . Two vicinal cysteines confer a peculiar redox regulation to low molecular weight protein tyrosine phosphatase in response to platelet-derived growth factor receptor stimulation. J Biol Chem. 2001; 276(36):33478-87. DOI: 10.1074/jbc.M102302200. View

Lambeth J . Nox/Duox family of nicotinamide adenine dinucleotide (phosphate) oxidases. Curr Opin Hematol. 2001; 9(1):11-7. DOI: 10.1097/00062752-200201000-00003. View

Cheng G, Cao Z, Xu X, Van Meir E, Lambeth J . Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene. 2001; 269(1-2):131-40. DOI: 10.1016/s0378-1119(01)00449-8. View

Morse D, Duncan H, Hooker N, Morse A . Hydrogen peroxide induces spawning in mollusks, with activation of prostaglandin endoperoxide synthetase. Science. 1977; 196(4287):298-300. DOI: 10.1126/science.403609. View

Sayre L, Arora P, Iyer R, Salomon R . Pyrrole formation from 4-hydroxynonenal and primary amines. Chem Res Toxicol. 1993; 6(1):19-22. DOI: 10.1021/tx00031a002. View

10.

Hochstein P . Futile redox cycling: implications for oxygen radical toxicity. Fundam Appl Toxicol. 1983; 3(4):215-7. DOI: 10.1016/s0272-0590(83)80128-6. View

11.

Forman H . Use and abuse of exogenous H2O2 in studies of signal transduction. Free Radic Biol Med. 2007; 42(7):926-32. PMC: 1945171. DOI: 10.1016/j.freeradbiomed.2007.01.011. View

12.

Forman H, Kennedy J . Role of superoxide radical in mitochondrial dehydrogenase reactions. Biochem Biophys Res Commun. 1974; 60(3):1044-50. DOI: 10.1016/0006-291x(74)90418-5. View

13.

Barrett W, DeGnore J, Keng Y, Zhang Z, Yim M, Chock P . Roles of superoxide radical anion in signal transduction mediated by reversible regulation of protein-tyrosine phosphatase 1B. J Biol Chem. 1999; 274(49):34543-6. DOI: 10.1074/jbc.274.49.34543. View

14.

Buettner G, Ng C, Wang M, Rodgers V, Schafer F . A new paradigm: manganese superoxide dismutase influences the production of H2O2 in cells and thereby their biological state. Free Radic Biol Med. 2006; 41(8):1338-50. PMC: 2443724. DOI: 10.1016/j.freeradbiomed.2006.07.015. View

15.

Ferrari D, SOLING H . The protein disulphide-isomerase family: unravelling a string of folds. Biochem J. 1999; 339 ( Pt 1):1-10. PMC: 1220120. View

16.

Hawkins B, Madesh M, Kirkpatrick C, Fisher A . Superoxide flux in endothelial cells via the chloride channel-3 mediates intracellular signaling. Mol Biol Cell. 2007; 18(6):2002-12. PMC: 1877121. DOI: 10.1091/mbc.e06-09-0830. View

17.

Spycher S, Tabataba-Vakili S, ODonnell V, Palomba L, Azzi A . 4-hydroxy-2,3-trans-nonenal induces transcription and expression of aldose reductase. Biochem Biophys Res Commun. 1996; 226(2):512-6. DOI: 10.1006/bbrc.1996.1386. View

18.

Lee S, Yang K, Kwon J, Lee C, Jeong W, Rhee S . Reversible inactivation of the tumor suppressor PTEN by H2O2. J Biol Chem. 2002; 277(23):20336-42. DOI: 10.1074/jbc.M111899200. View

19.

Halvey P, Watson W, Hansen J, Go Y, Samali A, Jones D . Compartmental oxidation of thiol-disulphide redox couples during epidermal growth factor signalling. Biochem J. 2005; 386(Pt 2):215-9. PMC: 1134784. DOI: 10.1042/BJ20041829. View

20.

Parola M, ROBINO G, Marra F, Pinzani M, Bellomo G, Leonarduzzi G . HNE interacts directly with JNK isoforms in human hepatic stellate cells. J Clin Invest. 1998; 102(11):1942-50. PMC: 509146. DOI: 10.1172/JCI1413. View