Skip to main content
SpringerLink
Log in
Book cover

Lipid Mediators and Their Metabolism in the Brain pp 159–191Cite as

Neurochemical Aspects of 4-Hydroxynonenal

  • Chapter
  • First Online:

Abstract

4-Hydroxynonenal (4-HNE) is a major end-product of peroxidation of membrane arachidonic acid (ARA). This nine carbon α, β-unsaturated aldehyde contains three functional groups, which often act in concert and help to explain its high reactivity (Poli and Schaur, 2000). Most importantly, there is a conjugated system of a C=C double bond and a C=O carbonyl group which provide a partial positive charge to carbon 3 due to the presence of mobile pi-electrons. This positive charge is further enhanced by the inductive effect of the hydroxy group at carbon 4. Therefore, 4-HNE is considered to be soft electrophiles and is prone to be attacked by nucleophiles, such as thiol or amino groups. This reaction occurs primarily at carbon 3 and secondarily at the carbonyl carbon 1.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Alary J., Debrauwer L., Fernandez Y., Cravedi J. P., Rao D., and Bories, G. (1998). 1,4-Dihydroxynonene mercapturic acid, the major end metabolite of exogenous 4-hydroxy-2-nonenal, is a physiological component of rat and human urine. Chem. Res. Toxicol. 11:130–135.

    Article  PubMed  CAS  Google Scholar 

  • Alin P., Danielson U.H., and Mannervik B. (1985). 4-Hydroxyalk-2-enals are substrates for glutathione transferase. FEBS Lett. 179:267–270.

    Article  PubMed  CAS  Google Scholar 

  • Almer G., Guegan C., Teismann P., Naini A., Rosoklija G., Hays A. P., Chen C. P., and Przedborski S. (2001). Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. Ann. Neurol. 49:176–185.

    Article  PubMed  CAS  Google Scholar 

  • Andreoletti O., Levavasseur E., Uro-Coste E., Tabouret G., Sarradin P., Delisle M.B., Berthon P., Salvayre R., Schelcher., and Negre-Salvayre A. (2002). Astrocytes accumulate 4-hydroxynonenal adducts in murine scrapie and human Creutzfeldt-Jakob disease. Neurobiol. Dis. 11:386–393.

    Google Scholar 

  • Ansari M.A., Roberts K.N., and Scheff.W. (2008). Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury. Free Radic. Biol. Med. 45:443–452.

    Article  PubMed  CAS  Google Scholar 

  • Arundine M. and Tymianski M. (2004). Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol. Life Sci. 61:657–668.

    Article  PubMed  CAS  Google Scholar 

  • Bacot S., Bernoud-Hubac N., Chantegrel B., Deshayes C., Doutheau A., Ponsin G., Lagarde M., and Guichardant M. (2007). Evidence for in situ ethanolamine phospholipid adducts with hydroxy-alkenals. J. Lipid Res. 48:816–825.

    Article  PubMed  CAS  Google Scholar 

  • Baler R., Dahl G., and Voellmy R. (1993). Activation of human heat shock genes is accompanied by oligomerization, modification, and rapid translocation of heat shock transcription factor HSF1. Mol. Cell Biol. 13:2486–2496.

    PubMed  CAS  Google Scholar 

  • Barrera G., Pizzimenti S., and Dianzani M.U. (2004). 4-hydroxynonenal and regulation of cell cycle: effects on the pRb/E2F pathway. Free Radic. Biol. Med. 37:597–606.

    Article  PubMed  CAS  Google Scholar 

  • Beal M.F. (1998). Mitochondrial dysfunction in neurodegenerative diseases. Biochim. Biophys. Acta. 1366:211–223.

    Article  PubMed  CAS  Google Scholar 

  • Beaulieu J.M. and Julien J.P. (2003). Peripherin-mediated death of motor neurons rescued by overexpression of neurofilament NF-H proteins. J. Neurochem. 85:248–256.

    Article  PubMed  CAS  Google Scholar 

  • Blanc E.M., Keller J.N., Fernandez S., and Mattson M.P. (1998). 4-hydroxynonenal, a lipid peroxidation product, impairs glutamate transport in cortical astrocytes. Glia. 22:149–160.

    Article  PubMed  CAS  Google Scholar 

  • Bradley M.A., Markesbery W.R., and Lovell M.A. (2010). Increased levels of 4-hydroxynonenal and acrolein in the brain in preclinical Alzheimer disease. Free Radic. Biol. Med. 48:1570–1576.

    Article  PubMed  CAS  Google Scholar 

  • Bramlett H.M., and Dietrich W.D. (2004). Pathophysiology of cerebral ischemia and brain trauma: similarities and differences. J. Cereb. Blood Flow Metab. 24:133–150.

    Article  PubMed  Google Scholar 

  • Burczynski M.E., Sridhar G.R., Palackal N.T., and Penning T.M. (2001). The reactive oxygen species--and Michael acceptor-inducible human aldo-keto reductase AKR1C1 reduces the alpha,beta-unsaturated aldehyde 4-hydroxy-2-nonenal to 1,4-dihydroxy-2-nonene. J Biol Chem. 276:2890–2897.

    Article  PubMed  CAS  Google Scholar 

  • Butterfield D.A., Bader Lange M.L., and Sultana R. (2010). Involvements of the lipid peroxidation product, HNE, in the pathogenesis and progression of Alzheimer’s disease. Biochim. Biophys. Acta. 1801:924–929.

    PubMed  CAS  Google Scholar 

  • Camandola S., Poli G., and Mattson M.P. (2000) The lipid peroxidation product 4-hydroxy-2,3-nonenal increases AP-1-binding activity through caspase activation in neurons. J. Neurochem. 74:159–68.

    Article  PubMed  CAS  Google Scholar 

  • Chaudhary P., Sharma R., Sharma A., Vatsyayan R., Yadav S., Singhal S.S., Rauniyar N., Prokai L., Awasthi S., and Awasthi Y.C. (2010). Mechanisms of 4-hydroxy-2-nonenal induced pro- and anti-apoptotic signaling. Biochemistry. 49:6263–6275.

    Article  PubMed  CAS  Google Scholar 

  • Chen Y.-R., Wang X., Templeton D., Davis R.J., and Tan T-H (1996). The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation. J Biol Chem 271:31929–31936.

    Article  PubMed  CAS  Google Scholar 

  • Chen H.J.C., Gonzalez F.J., Shou M.G., and Chung F.L. (1998). 2,3-Epoxy-4-hydroxynonenal, a potential lipid peroxidation product for etheno adduct formation, is not a substrate of human epoxide hydrolase. Carcinogenesis 19, 939–943.

    Article  PubMed  CAS  Google Scholar 

  • Chen Z.H., Saito Y., Yoshida Y., Sekine A., Noguchi N., and Niki E. (2005). 4-Hydroxynonenal induces adaptive response and enhances PC12 cell tolerance primarily through induction of thioredoxin reductase 1 via activation of Nrf2. J. Biol. Chem. 280:41921–41927.

    Article  PubMed  CAS  Google Scholar 

  • Cheng J.Z., Singhal S.S., Sharma A., Saini M., Yang Y., Awasthi S., Zimniak P., and Awasthi Y.C. (2001) Transfection of mGSTA4 in HL-60 cells protects against 4-hydroxynonenal-induced apoptosis by inhibiting JNK-mediated signaling. Arch Biochem Biophys. 392:197–207.

    Article  PubMed  CAS  Google Scholar 

  • Choudhury S., Pan J., Amin S., Chung F.L., and Roy R. (2004). Repair kinetics of trans-4-hydroxynonenal-induced cyclic 1,N2-propanodeoxyguanine DNA adducts by human cell nuclear extracts. Biochemistry 43:7514–7521.

    Article  PubMed  CAS  Google Scholar 

  • Chung F.L., Chen H.J., and Nath R.G. (1996). Lipid peroxidation as a potential endogenous source for the formation of exocyclic DNA adducts. Carcinogenesis 17:2105–2111.

    Article  PubMed  CAS  Google Scholar 

  • Cohen G.M. (1997). Caspases: the executioners of apoptosis. Biochem. J. 326: 1–16.

    PubMed  CAS  Google Scholar 

  • Coux O, Tanka K, and Goldberg A.L. (1996). Structure and functions of the 20 S and 26 S proteosomes. Annu Rev. Biochem. 65:801–847.

    Article  PubMed  CAS  Google Scholar 

  • Creagh E.M., Conroy H., Martin S.J. (2003). Caspase-activation pathways in apoptosis and immunity. Immunol Rev. 193:10–21.

    Article  PubMed  CAS  Google Scholar 

  • Davis R.J. (1999). Signal transduction by the c-Jun N-terminal kinase. Biochem. Soc. Transduc. 64:1–12.

    CAS  Google Scholar 

  • Drake J., Petroze R., Castegna A., Ding Q., Keller J.N., Markebery W.R., Lovell M.A., and Butterfield D.A. (2004). 4-Hydroxynonenal oxidatively modifies histones: implications for Alzheimer’s disease. Neurosci. Lett. 356:155–158.

    Article  PubMed  CAS  Google Scholar 

  • Esterbauer H., Schaur R.J., and Zollner H. (1991). Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11:81–128.

    Article  PubMed  CAS  Google Scholar 

  • Farooqui A.A., and Horrocks L.A. (1994). Excitotoxicity and neurological disorders: involvement of membrane phospholipids. Int. Rev. Neurobiol. 36:267–323.

    Article  PubMed  CAS  Google Scholar 

  • Farooqui A.A., Ong W.Y., Lu X.R., Halliwell B., and Horrocks L.A. (2001). Neurochemical consequences of kainate-induced toxicity in brain: involvement of arachidonic acid release and prevention of toxicity by phospholipase A2 inhibitors.Brain Res. Rev. 38: 61–78.

    Google Scholar 

  • Farooqui A. A. and Horrocks L. A. (2007). Glycerophospholipids in the Brain: Phospholipases A2 in Neurological Disorders, pp. 1-394. Springer, New York.

    Google Scholar 

  • Farooqui A.A., Ong W.Y., and Horrocks L.A. (2008). Excitatory amino acid receptors in brain in Neurochemical Aspects of Excitotoxicity. Springer New York.

    Google Scholar 

  • Farooqui A.A. (2009). Hot Topics in Neural Membrane Lipidology. Springer, New York.

    Google Scholar 

  • Farooqui A.A. (2010). Neurochemical Aspects of Neurotraumatic and Neurodegenerative Diseases. Springer, New York.

    Book  Google Scholar 

  • Farooqui A.A., Ong W.Y., and Farooqui T. (2010). Lipid mediators in the nucleus: Their potential contribution to Alzheimer’s disease. Biochim Biophys Acta. 1801:906–916.

    Book  Google Scholar 

  • Ferrington D.A., and Kapphahn R.J. (2004). Catalytic site-specific inhibition of the 20 S proteasome by 4-hydroxynonenal. FEBS Lett 578:217–223.

    Article  PubMed  CAS  Google Scholar 

  • Friguet B. (2006). Oxidized protein degradation and repair in ageing and oxidative stress. FEBS Lett 580:2910–2916.

    Article  PubMed  CAS  Google Scholar 

  • Gallagher E.P., and Gardner J.L. (2002). Comparative expression of two alpha class glutathione S-transferases in human adult and prenatal liver tissues. Biochem Pharmacol. 63:2025–2036.

    Article  PubMed  CAS  Google Scholar 

  • Gard A.L., Solodushko V.G., Waeg G., and Majic T. (2001). 4-Hydroxynonenal, a lipid peroxidation byproduct of spinal cord injury, is cytotoxic for oligodendrocyte progenitors and inhibits their responsiveness to PDGF. Microsc. Res. Tech. 52:709–718.

    Article  PubMed  CAS  Google Scholar 

  • Gardner J.L., Doi A.M., Pham R.T., Huisden C.M., and Gallagher E.P. (2003). Ontogenic differences in human liver 4-hydroxynonenal detoxification are associated with in vitro injury to fetal hematopoietic stem cells. Toxicol Appl Pharmacol. 191:95–106.

    Article  PubMed  CAS  Google Scholar 

  • Graham D.G. (1978). Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol. 14:633–643.

    PubMed  CAS  Google Scholar 

  • Grune T., and Davies K.J. (2003). The proteasomal system and HNE modified proteins. Mol Aspects Med 24:195–204.

    Google Scholar 

  • Gu X., Zhang W., Salomon R. G. (2007). Fe2+ catalyzes vitamin E-induced fragmentation of hydroperoxy and hydroxy endoperoxides that generates gamma-hydroxy alkenals. J. Am. Chem. Soc. 129:6088–6089.

    Article  PubMed  CAS  Google Scholar 

  • Guichardant M., Bernoud-Hubac N., Chantegrel B., Deshayes C., and Lagarde M. (2002). Aldehydes from n-6 fatty acid peroxidation. Effects on aminophospholipids. Prostaglandins Leukot Essent Fatty Acids. 67:147–149.

    Article  PubMed  CAS  Google Scholar 

  • Hahn G.M., and Li G.C. (1982). Thermotolerance and heat shock proteins in mammalian cells. Radiat. Res. 92:452–457.

    Article  PubMed  CAS  Google Scholar 

  • Han J., Lee J.-D., Bibbs L., and Ulevitch R.J. (1994). A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science (Wash DC) 265:808–811.

    Article  CAS  Google Scholar 

  • Hou L., Honaker M.T., Shireman L.M., Balogh L.M., Roberts A.G., Ng K.C., Nath A., and Atkins W.M. (2007). Functional promiscuity correlates with conformational heterogeneity in A-class glutathione S-transferases. J Biol Chem. 282:23264–232674.

    Article  PubMed  CAS  Google Scholar 

  • Howard M.K., Burke L.C., Mailhos C., Pizzey A., Gilbert C.S., Lawson W.D., Collins M.K., Thomas N.S., and Latchman D.S. (1993). Cell cycle arrest of proliferating neuronal cells by serum deprivation can result in either apoptosis or differentiation. J. Neurochem. 60:1783–1791.

    Article  PubMed  CAS  Google Scholar 

  • Jacobs A.T. and Marnett L.J. (2007). Heat shock factor 1 attenuates 4-Hydroxynonenal-mediated apoptosis: critical role for heat shock protein 70 induction and stabilization of Bcl-XL. J. Biol. Chem. 282:33412–33420.

    Article  PubMed  CAS  Google Scholar 

  • Jacobs A.T. and Marnett L.J. (2009). HSF1-mediated BAG3 expression attenuates apoptosis in 4-hydroxynonenal-treated colon cancer cells via stabilization of anti-apoptotic Bcl-2 proteins. J. Biol. Chem. 284:9176–9183.

    Article  PubMed  CAS  Google Scholar 

  • Jenner P., and Olanow C.W. (2006). The pathogenesis of cell death in Parkinson’s disease. Neurology. 66(10 Suppl 4):S24–S36.

    PubMed  Google Scholar 

  • Jeong W.S., Jun M., and Kong A.N. (2006). Nrf2: a potential molecular target for cancer chemoprevention by natural compounds. Antioxid. Redox Signal 8:99-106.

    Article  PubMed  CAS  Google Scholar 

  • Kadoya A., Miyake H., and Ohyashiki T. (2003). Contribution of lipid dynamics on the inhibition of bovine brain synaptosomal Na+-K+-ATPase activity induced by 4-hydroxy-2-nonenal. Biol. Pharm. Bull. 26:787–793.

    Article  PubMed  CAS  Google Scholar 

  • Kanfer J.N., Sorrentino G., and Sitar D.S. (1998). Phospholipases as mediators of amyloid beta peptide neurotoxicity: an early event contributing to neurodegeneration characteristic of Alzheimer’s disease. Neurosci Lett. 257:93–96.

    Article  PubMed  CAS  Google Scholar 

  • Karin M. (1995). The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 270:16483–16486.

    PubMed  CAS  Google Scholar 

  • Kim J., Kim T.Y., Hwang J.J., Lee J.Y., Shin J.H., Gwag B.J., and Koh J.Y. (2009). Accumulation of labile zinc in neurons and astrocytes in the spinal cords of G93A SOD-1 transgenic mice. Neurobiol Dis. 34:221–229.

    Article  PubMed  CAS  Google Scholar 

  • Klussmann S. and Martin-Villalba A. (2005). Molecular targets in spinal cord injury. J. Mol. Med. 83:657–671.

    Article  PubMed  CAS  Google Scholar 

  • Kristal B.S., Park B.K., and Yu B.P. (1996). 4-Hydroxyhexenal is a potent inducer of the mitochondrial permeability transition. J. Biol. Chem. 271:6033–6038.

    Article  PubMed  CAS  Google Scholar 

  • Kutuk O. and Basaga H. (2007). Apoptosis signalling by 4-hydroxynonenal: a role for JNK-c-Jun/AP-1 pathway. Redox Rep. 12:30–34.

    Article  PubMed  CAS  Google Scholar 

  • Kyriakis J.M., Banerjee P., Nikolakaki E., Dai T., Ruble E.A., Ahmad M.F., Avruch J., and Woodgett J.R. (1994). The stress-activated protein kinase subfamily of c-Jun kinases. Nature (Lond) 369:156–160.

    Article  CAS  Google Scholar 

  • Lee S.. H.; Oe T., and Blair I. A. (2001). Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins. Science 292:2083–2086.

    Article  PubMed  CAS  Google Scholar 

  • Lee J.Y., Je J.H., Jung K.J., Yu B.P., and Chung H.Y. (2004). Induction of endothelial iNOS by 4-hydroxyhexenal through NF-kappaB activation. Free Radic. Biol. Med. 37:539–548.

    Article  PubMed  CAS  Google Scholar 

  • Lee S.J., Kim C.E., Yun M.R., Seo K.W., Park H.M., Yun J.W., Shin H.K., Bae S.S., and Kim C.D. (2010). 4-Hydroxynonenal enhances MMP-9 production in murine macrophages via 5-lipoxygenase-mediated activation of ERK and p38 MAPK. Toxicol. App. Pharmacol. 242:191–198.

    Article  CAS  Google Scholar 

  • Leonarduzzi G., Robbesyn F., and Poli G. (2004). Signaling kinases modulated by 4-hydroxynonenal. Free Radic Biol Med. 37:1694–1702.

    Article  PubMed  CAS  Google Scholar 

  • Liu R., Li B., Flanagan S.W., Oberley L.W., Gozal D., and Oiu M. (2002). Increased mitochondrial antioxidative activity or decreased oxygen free radical propagation prevent mutant SOD1-mediated motor neuron cell death and increase amyotrophic lateral sclerosis-like transgenic mouse survival. J. Neurochem. 80:488–500.

    Article  PubMed  CAS  Google Scholar 

  • Lu C., Chan S.L., Haughey N., Lee W.T., and Mattson M.P. (2001). Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2,3-nonenal on N-methyl-D-aspartate channels. J. Neurochem. 78:577–589.

    Article  PubMed  CAS  Google Scholar 

  • Lu C., Chan S.L., Fu W., and Mattson M.P. (2002). The lipid peroxidation product 4-hydroxynonenal facilitates opening of voltage-dependent Ca2+ channels in neurons by increasing protein tyrosine phosphorylation. J. Biol. Chem. 277:24368–24375.

    Article  PubMed  CAS  Google Scholar 

  • Mark R.J., Lovell M.A., Markesbery W.R., Uchida K., and Mattson M.P. (1997). A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J. Neurochem. 68:255–264.

    Article  PubMed  CAS  Google Scholar 

  • McKracken E., Graham D.I., Nilsen M., Stewart J., Nicoll J.A., and Horsburgh K. (2001). 4-Hydroxynonenal immunoreactivity is increased in human hippocampus after global ischemia. Brain Path. 11:14–21.

    Google Scholar 

  • Mertsch K., Blasig I., and Grune T. (2001). 4-Hydroxynonenal impairs the permeability of an in vitro rat blood-brain barrier. Neurosci Lett. 314:135–138.

    Article  PubMed  CAS  Google Scholar 

  • Mitchell D.Y. and Petersen D.R. (1987). The oxidation of alpha-beta unsaturated aldehydic products of lipid peroxidation by rat liver aldehyde dehydrogenases. Toxicol. Appl. Pharmacol. 87:403–410.

    Article  PubMed  CAS  Google Scholar 

  • Mitchell D.Y., and Petersen D.R. (1991). Inhibition of rat hepatic mitochondrial aldehyde dehydrogenase-mediated acetaldehyde oxidation by trans-4-hydroxy-2-nonenal. Hepatology 13:728–734.

    PubMed  CAS  Google Scholar 

  • Muralikrishna Adibhatla R., and Hatcher J.F. (2006). Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Radic Biol Med. 40:376–387.

    Article  CAS  Google Scholar 

  • Nadkarni D.V. and Sayre L.M. (1995). Structural definition of early lysine and histidine adduction chemistry of 4-hydroxynonenal. Chem. Res. Toxicol. 8:284–291.

    Article  PubMed  CAS  Google Scholar 

  • Okada K., Wangpoengtrakul C., Osawa T., Toyokuni S., Tanaka K., Ushida K. (1999). 4-Hydroxy-2-nonenal-mediated impairment of intracellular proteolysis during oxidative stress. Identification of proteasomes as target molecules. J. Biol. Chem. 274: 23787–23793.

    Article  PubMed  CAS  Google Scholar 

  • Ong W. Y., Lu X. R., Hu C. Y., and Halliwell B. (2000). Distribution of hydroxynonenal-modified proteins in the kainate-lesioned rat hippocampus: evidence that hydroxynonenal formation precedes neuronal cell death. Free Radic. Biol. Med. 28:1214–1221.

    Article  PubMed  CAS  Google Scholar 

  • Panter S. S., Yum S. W., and Faden A. I. (1990). Alteration in extracellular amino acids after traumatic spinal cord injury. Ann. Neurol. 27:96–99.

    Article  PubMed  CAS  Google Scholar 

  • Pavel J., Lukácová N., Marsala J., and Marsala M. (2001). The regional changes of the catalytic NOS activity in the spinal cord of the rabbit after repeated sublethal ischemia. Neurochem Res. 26:833–839.

    Article  PubMed  CAS  Google Scholar 

  • Perluigi M., Fai Poon H., Hensley K., Pieree W.M., Klein J.B., Calabrese V., De Marco C., and Butterfield D.A. (2005). Proteomic analysis of 4-hydroxy-2-nonenal-modified proteins in G93A-SOD1 transgenic mice--a model of familial amyotrophic lateral sclerosis. Free Radic. Biol. Med. 38:960–968.

    Article  PubMed  CAS  Google Scholar 

  • Perluigi M., Sultana R., Cenini G., Di Domenico F., Memo M., Pierce W.M., Coccia R., and Butterfield D.A. (2009). Redox proteomics identification of 4-hydroxynonenal-modified brain proteins in Alzheimer’s disease: Role of lipid peroxidation in Alzheimer’s disease pathogenesis. Proteomics Clin. Appl. 3:682–693.

    Article  PubMed  CAS  Google Scholar 

  • Petersen D.R. and Doorn J.A. (2004). Reactions of 4-hydroxynonenal with proteins and cellular targets. Free Radicals in Biol. Med. 37:937–945.

    Article  CAS  Google Scholar 

  • Pflanzner T., Kuhlmann C.R., and Pietrzik C.U. (2010). Blood-Brain-Barrier Models for the Investigation of Transporter- and Receptor-Mediated Amyloid-beta Clearance in Alzheimer’s Disease. Curr. Alzheimer Res. Aug 2. [Epub ahead of print].

    Google Scholar 

  • Picklo M.J., Amarnath V., McIntyre J.O., Graham D.G., and Montine T.J. (1999). 4-Hydroxy-2(E)-nonenal inhibits CNS mitochondrial respiration at multiple sites. J Neurochem. 72:1617–1624.

    Article  PubMed  CAS  Google Scholar 

  • Plum G. E., Grollman A. P., Johnson F., and Breslauer K. J. (1992). Influence of an exocyclic guanine adduct on the thermal stability, conformation, and melting thermodynamics of a DNA duplex. Biochemistry 31: 12096–12102.

    Article  PubMed  CAS  Google Scholar 

  • Poli G., and Schaur R.J. (2000). 4-Hydroxynonenal in the pathomechanisms of oxidative stress. IUBMB Life. 50:315–321.

    Article  PubMed  CAS  Google Scholar 

  • Poli G., Biasi F., and Leonarduzzi G. (2006). 4-Hydroxynonenal-protein adducts: A reliable biomarker of lipid oxidation in liver diseases. Mol. Aspects Med. 29:67–71.

    Article  CAS  Google Scholar 

  • Qin Z., Hu D., Han S., Reaney S.H., Di Monte D.A., and Fink A.L. (2007). Effect of 4-hydroxy-2-nonenal modification on alpha-synuclein aggregation.J. Biol. Chem. 282:5862–5870.

    CAS  Google Scholar 

  • Raghupathi R. (2004). Cell death mechanisms following traumatic brain injury. Brain Path. 14:215–222.

    Article  Google Scholar 

  • Raingeaud J., Gupta S., Rogers J.S., Dickens M., Han J., Ulevitch R.J., and Davis R.J. (1995). Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J. Biol. Chem. 270:7420–7426.

    Article  PubMed  CAS  Google Scholar 

  • Raza H., John A., Brown E.M., Benedict S., and Kambal S. (2008). Alterations in mitochondrial respiratory functions, redox metabolism and apoptosis by oxidant 4-hydroxynonenal and antioxidants curcumin and melatonin in PC12 cells. Toxicol. Appl. Pharmacol. 226:161–168.

    Article  PubMed  CAS  Google Scholar 

  • Ray S.K., Hogan E.L., and Banik N.L. (2003). Calpain in the pathophysiology of spinal cord injury: neuroprotection with calpain inhibitors. Brain Res. Rev. 42:169–185.

    Article  PubMed  CAS  Google Scholar 

  • Rockwell P., Yuan H., Magnusson R., and Figueiredo-Pereira M.E. (2000). Proteasome inhibition in neuronal cells induces a proinflammatory response manifested by upregulation of cyclooxygenase-2, its accumulation as ubiquitin conjugates, and production of the prostaglandin PGE2. Arch. Biochem. Biophys. 374:325–333.

    Article  PubMed  CAS  Google Scholar 

  • Rossi M.A., Di Mauro C., Dianzani M.U. (1993). Action of lipid peroxidation products on phosphoinositide specific phospholipase C. Mol. Aspects Med. 14:273–279.

    Article  PubMed  CAS  Google Scholar 

  • Salomoni P. and Khelifi A.F. (2006). Daxx: death or survival protein? Trends Cell Biol. 16:97–104.

    Article  PubMed  CAS  Google Scholar 

  • Sarge K.D., Murphy S.P., and Morimoto R.I. (1993). Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress. Mol Cell Biol. 13:1392–1407.

    Google Scholar 

  • Schaur R.J. (2003). Basic aspects of the biochemical reactivity of 4-hydroxynonenal. Mol. Aspects Med. 24:149–159.

    Article  CAS  Google Scholar 

  • Schneider C., Tallman K.A., Porter N.A., and Brash A.R. (2001). Two distinct pathways of formation of 4-hydroxynonenal mechanisms of nonenzymatic transformation of the 9- and 13-hydroperoxides of linoleic acid to 4-hydroxyalkenals. J. Biol. Chem. 276:20831–20838.

    Article  PubMed  CAS  Google Scholar 

  • Schneider C., Porter N.A., and Brash A.R. (2004). Autoxidative transformation of chiral omega6 hydroxy linoleic and arachidonic acids to chiral 4-hydroxy-2E-nonenal. Chem. Res. Toxicol. 17:937–941.

    Article  PubMed  CAS  Google Scholar 

  • Schneider C., Porter N. A., and Brash A. R. (2008). Routes to 4-hydroxynonenal: fundamental issues in the mechanisms of lipid peroxidation. J. Biol. Chem. 283:15539–15543.

    Article  PubMed  CAS  Google Scholar 

  • Seet R.C., Lee C.Y., Lim E.C., Tan J.J., Quek A.M., Chong W.L., Looi W.F., Huang S.H., Wang H., Chan Y.H., and Halliwell B. (2009). Oxidative damage in Parkinson disease: Measurement using accurate biomarkers. Free Radic Biol Med. 2009 Dec 4. [Epub ahead of print].

    Google Scholar 

  • Selley M.L. (1998). (E)-4-hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson’s disease. Free Radic Biol Med. 25:169–174.

    Article  PubMed  CAS  Google Scholar 

  • Sharma R., Yang Y., Sharma A., Awasthi S., and Awasthi Y.C. (2004). Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxid Redox Signal 6:289–300.

    Article  PubMed  CAS  Google Scholar 

  • Sharma R., Sharma A., Dwivedi S., Zimniak P., Awasthi S., Awasthi Y.C. (2008). 4-Hydroxynonenal self-limits fas-mediated DISC-independent apoptosis by promoting export of Daxx from the nucleus to the cytosol and its binding to Fas. Biochemistry 47:143–156.

    Article  PubMed  CAS  Google Scholar 

  • Shibata N., Kato Y., Inose Y., Hiroi A., Yamamoto T., Morikawa S., Sawada M., and Kobayashi M. (2010a). 4-Hydroxy-2-nonenal upregulates and phosphorylates cytosolic phospholipase A (2) in cultured Ra2 microglial cells via MAPK pathways. Neuropathology. 2010 Jul 27. [Epub ahead of print].

    Google Scholar 

  • Shibata N., Kakita A., Takahashi H., Ihara Y., Nobukuni K., Fujimura H., Sakoda S., and Kobayashi M. (2010b). Increased expression and activation of cytosolic phospholipase A(2) in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. Acta Neuropath 2010 Jan 12. [Epub ahead of print].

    Google Scholar 

  • Shibata N., Inose Y., Toi S., Hiroi A., Yamamoto T., and Kobayashi M. (2010c). Involvement of 4-hydroxy-2-nonenal accumulation in multiple system atrophy. Acta Histochem Cytochem. 43:69–75.

    Article  PubMed  CAS  Google Scholar 

  • Sitte N., Merker K., Von Zglinicki T., Grune T., and Davies K.J. (2000). Protein oxidation and degradation during cellular senescence of human BJ fibroblasts: part I—effects of proliferative senescence. FASEB J. 14:2495–2502.

    Article  PubMed  CAS  Google Scholar 

  • Song B.J., Soh Y., Bae M., Pie J., Wan J., and Jeong K. (2001). Apoptosis of PC12 cells by 4-hydroxy-2-nonenal is mediated through selective activation of the c-Jun N-terminal protein kinase pathway. Chem Biol Interact. 130-132:943–954.

    Article  PubMed  Google Scholar 

  • Springer JE, Azbill RD, Mark RJ, Begley JG, Waeg G, Mattson MP. (1997). 4-hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake. J Neurochem. 68:2469–2476.

    Article  PubMed  CAS  Google Scholar 

  • Srivastava S., Watowich S.J., Petrash J.M., Srivastava S.K., and Bhatnagar A. (1999). Structural and kinetic determinants of aldehyde reduction by aldose reductase. Biochemistry 38:42–54.

    Article  PubMed  CAS  Google Scholar 

  • Sundström E. and Mo L. L. (2002). Mechanisms of glutamate release in the rat spinal cord slices during metabolic inhibition. J. Neurotrauma 19:257–266.

    Article  PubMed  Google Scholar 

  • Tamagno E., Robino G., Obbili A., Bardini P., Aragno M., Parola M., and Danni O. (2003). H2O2 and 4-hydroxynonenal mediate amyloid beta-induced neuronal apoptosis by activating JNKs and p38MAPK. Exp. Neurol. 180:144–155.

    Article  PubMed  CAS  Google Scholar 

  • Trevisani M., Siemens J., Materazzi S., Bautista D.M., Nassini R., Campi B., Imamachi N., Andrè E., Patacchini R., Cottrell G.S., Gatti R., Basbaum A.I., Bunnett N.W., Julius D., and Geppetti P. (2007). 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci USA. 104:13519–13524.

    Article  PubMed  CAS  Google Scholar 

  • Uchida K. (2003). 4-Hydroxy-2-nonenal: a product and mediator of oxidative stress. Prog. Lipid Res. 42:318–343.

    Article  PubMed  CAS  Google Scholar 

  • Vaishnav R.A., Singh I.N., Miller D.M., and Hall E.D. (2010). Lipid peroxidation-derived reactive aldehydes directly and differentially impair spinal cord and brain mitochondrial function. J Neurotrauma. 27:1311–1320.

    Article  PubMed  Google Scholar 

  • Vieira O., Escargueil-Blanc I., Jurgens G., Borner C., Almeida L., Salvayre R. and Negre-Salvayre A. (2000). Oxidized LDLs alter the activity of the ubiquitin–proteasome pathway: potential role in oxidized LDL-induced apoptosis. FASEB J 14: 532–542.

    PubMed  CAS  Google Scholar 

  • Vigh L., Smith R.G., Soós J., Engelhardt J.I., Appel S.H., and Siklós L. (2005). Sublethal dose of 4-hydroxynonenal reduces intracellular calcium in surviving motor neurons in vivo. Acta Neuropathol. 109:567–575.

    Article  PubMed  CAS  Google Scholar 

  • Wacker M., Chhuler D., Wanek P., and Eder E. (2000). Development of a 32P-postlabeling method for the detection of 1,N(2)-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal in vivo. Chem. Res. Toxicol. 13:1165-1173.

    Article  PubMed  CAS  Google Scholar 

  • Wang H., Kozekov I.D., Harris T.M., and Rizzo C.J. (2003). Site-specific synthesis and reactivity of oligonucleotides containing stereochemically defined 1,N 2-deoxyguanosine adducts of the lipid peroxidation product trans-4-hydroxynonenal. J. Am. Chem. Soc. 125:5687–5700.

    Article  PubMed  CAS  Google Scholar 

  • Wang R., Malter J.S., and Wang D.S. (2010). N-Acetylcysteine Prevents 4-Hydroxynonenal- and Amyloid-beta-Induced Modification and Inactivation of Neprilysin in SH-SY5Y Cells. J. Alzheimer Res. 19:179–189.

    Google Scholar 

  • Weisenseel J. P., Reddy G. R., Marnett L. J., and Stone M. P. (2002). Structure of an oligodeoxynucleotide containing a 1,N(2)-propanodeoxyguanosine adduct positioned in a palindrome derived from the Salmonella typhimurium hisD3052 gene: Hoogsteen pairing at pH 5.2. Chem. Res. Toxicol. 15:127–139.

    Article  PubMed  CAS  Google Scholar 

  • Williams T.I., Lynn B.C., Markesbery W.R., and Lovell M.A. (2006). Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer’s disease. Neurobiol. Aging 27:1094–1099.

    Article  PubMed  CAS  Google Scholar 

  • Yang X., Khosravi-Far R., Chang H.Y., and Baltimore D. (1997). Daxx, a novel Fas-binding protein that activates JNK and apoptosis. Cell. 89:1067–1076.

    Article  PubMed  CAS  Google Scholar 

  • Yang Y., Sharma R., Sharma A., Awasthi A., and Awasthi S. (2003). Lipid peroxidation and cell cycle signaling: 4-hydroxynonenal, a key molecule in stress mediated signaling. Acta Biochim. Pol. 50:319–336.

    PubMed  CAS  Google Scholar 

  • Yao X. (2009). Effect of zinc exposure on HNE and GLT-1 in spinal cord culture. Neurotoxicoloy. 30:121–126.

    Article  CAS  Google Scholar 

  • Yun S.W., Gerlach M., Riederer P., and Klein M.A. (2006). Oxidative stress in the brain at early preclinical stages of mouse scrapie. Exp Neurol. 201:90–98.

    Article  PubMed  CAS  Google Scholar 

  • Zarkovic K. (2003). 4-hydroxynonenal and neurodegenerative diseases. Mol. Aspects Med. 24:293–303.

    Article  PubMed  CAS  Google Scholar 

  • Zhang D., Dhillon H.S., Mattson M.P., Yurek D.M., and Prasad R.M. (1999). Immunohistochemical detection of the lipid peroxidation product 4-hydroxynonenal after experimental brain injury in the rat. Neurosci. Lett. 272:57–61.

    Article  PubMed  CAS  Google Scholar 

  • Zhou S.Y., and Decker, E.A. (1999). Ability of carnosine and other skeletal-muscle components to quench unsaturated aldehydic lipid oxidation-products. J. Agric. Food Chem. 47:51–55.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, 43210, USA

    Akhlaq A. Farooqui

Authors
  1. Akhlaq A. Farooqui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akhlaq A. Farooqui .

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Farooqui, A.A. (2011). Neurochemical Aspects of 4-Hydroxynonenal. In: Lipid Mediators and Their Metabolism in the Brain. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9940-5_6

Download citation

Publish with us

Policies and ethics

Search

Navigation