Regulation and therapeutic strategies of 4-hydroxy-2-nonenal metabolism in heart disease

References

• Uchida K. 4-Hydroxy-2-nonenal: a product and mediator of oxidative stress. Prog Lipid Res 2003;42:318–343.
   PubMed Web of Science ®Google Scholar
• Anderson EJ, Katunga LA, Willis MS. Mitochondria as a source and target of lipid peroxidation products in healthy and diseased heart. Clin Exp Pharmacol Physiol 2012;39: 179–193.
   PubMed Web of Science ®Google Scholar
• Roede JR, Jones DP. Reactive species and mitochondrial dysfunction: mechanistic significance of 4-hydroxynonenal. Environ Mol Mutagen 2010;51:380–390.
   PubMed Web of Science ®Google Scholar
• Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991;11:81–128.
   PubMed Web of Science ®Google Scholar
• Isom AL, Barnes S, Wilson L, Kirk M, Coward L, Darley-Usmar V. Modification of Cytochrome c by 4-hydroxy- 2-nonenal: evidence for histidine, lysine, and arginine-aldehyde adducts. J Am Soc Mass Spectrom 2004;15:1136–1147.
   PubMed Web of Science ®Google Scholar
• Bulteau AL, Lundberg KC, Humphries KM, Sadek HA, Szweda PA, Friguet B, Szweda LI. Oxidative modification and inactivation of the proteasome during coronary occlusion/reperfusion. J Biol Chem 2001;276:30057–30063.
   PubMed Web of Science ®Google Scholar
• Ferrington DA, Kapphahn RJ. Catalytic site-specific inhibition of the 20S proteasome by 4-hydroxynonenal. FEBS Lett 2004;578:217–223.
   PubMed Web of Science ®Google Scholar
• Farout L, Mary J, Vinh J, Szweda LI, Friguet B. Inactivation of the proteasome by 4-hydroxy-2-nonenal is site specific and dependant on 20S proteasome subtypes. Arch Biochem Biophys 2006;453:135–142.
   PubMed Web of Science ®Google Scholar
• Akude E, Zherebitskaya E, Roy Chowdhury SK, Girling K, Fernyhough P. 4-Hydroxy-2-nonenal induces mitochondrial dysfunction and aberrant axonal outgrowth in adult sensory neurons that mimics features of diabetic neuropathy. Neurotox Res 2010;17:28–38.
   PubMed Web of Science ®Google Scholar
• Kaplan P, Tatarkova Z, Racay P, Lehotsky J, Pavlikova M, Dobrota D. Oxidative modifications of cardiac mitochondria and inhibition of cytochrome c oxidase activity by 4-hydroxynonenal. Redox Rep 2007;12:211–218.
   PubMed Web of Science ®Google Scholar
• Keller JN, Mark RJ, Bruce AJ, Blanc E, Rothstein JD, Uchida K, et al. 4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neuroscience 1997;80:685–696.
   PubMed Web of Science ®Google Scholar
• Keith RJ, Haberzettl P, Vladykovskaya E, Hill BG, Kaiserova K, Srivastava S, et al. Aldose reductase decreases endoplasmic reticulum stress in ischemic hearts. Chem Biol Interact 2009;178:242–249.
   PubMed Web of Science ®Google Scholar
• Grimsrud PA, Xie H, Griffin TJ, Bernlohr DA. Oxidative stress and covalent modification of protein with bioactive aldehydes. J Biol Chem 2008;283:21837–21841.
   PubMed Web of Science ®Google Scholar
• Poli G, Schaur RJ, Siems WG, Leonarduzzi G. 4-hydroxynonenal: a membrane lipid oxidation product of medicinal interest. Med Res Rev 2008;28:569–631.
   PubMed Web of Science ®Google Scholar
• Uchida K, Stadtman ER. Covalent attachment of 4-hydroxynonenal to glyceraldehyde-3-phosphate dehydrogenase. A possible involvement of intra- and intermolecular cross-linking reaction. J Biol Chem 1993;268:6388–6393.
   PubMed Web of Science ®Google Scholar
• Roede JR, Carbone DL, Doorn JA, Kirichenko OV, Reigan P, Petersen DR. In vitro and in silico characterization of peroxiredoxin 6 modified by 4-hydroxynonenal and 4-oxononenal. Chem Res Toxicol 2008;21:2289–2299.
   PubMed Web of Science ®Google Scholar
• Uchida K. Role of reactive aldehyde in cardiovascular diseases. Free Radic Biol Med 2000;28:1685–1696.
   PubMed Web of Science ®Google Scholar
• Mattson MP. Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Exp Gerontol 2009;44:625–633.
   PubMed Web of Science ®Google Scholar
• Nakamura K, Kusano K, Nakamura Y, Kakishita M, Ohta K, Nagase S, et al. Carvedilol decreases elevated oxidative stress in human failing myocardium. Circulation 2002;105: 2867–2871.
   PubMed Web of Science ®Google Scholar
• Budas GR, Disatnik MH, Mochly-Rosen D. Aldehyde dehydrogenase 2 in cardiac protection: a new therapeutic target?Trends Cardiovasc Med 2009;19:158–164.
   PubMed Web of Science ®Google Scholar
• Blasig IE, Grune T, Schonheit K, Rohde E, Jakstadt M, Haseloff RF, Siems WG. 4-Hydroxynonenal, a novel indicator of lipid peroxidation for reperfusion injury of the myocardium. Am J Physiol 1995;269:H14–H22.
   PubMed Web of Science ®Google Scholar
• Dolinsky VW, Chan AY, Robillard Frayne I, Light PE, Des Rosiers C, Dyck JR. Resveratrol prevents the prohypertrophic effects of oxidative stress on LKB1. Circulation. 2009;119:1643–1652.
   PubMed Web of Science ®Google Scholar
• Kavazis AN, Smuder AJ, Min K, Tumer N, Powers SK. Short-term exercise training protects against doxorubicin-induced cardiac mitochondrial damage independent of HSP72. Am J Physiol Heart Circ Physiol 2010;299:H1515–H1524.
   PubMed Web of Science ®Google Scholar
• Lucas DT, Szweda LI. Declines in mitochondrial respiration during cardiac reperfusion: age-dependent inactivation of alpha-ketoglutarate dehydrogenase. Proc Natl Acad Sci U S A 1999;96:6689–6693.
   PubMed Web of Science ®Google Scholar
• Asselin C, Shi Y, Clement R, Tardif JC, Des Rosiers C. Higher circulating 4-hydroxynonenal-protein thioether adducts correlate with more severe diastolic dysfunction in spontaneously hypertensive rats. Redox Rep 2007;12:68–72.
   PubMed Web of Science ®Google Scholar
• Chen JJ, Schenker S, Henderson GI. 4-hydroxynonenal levels are enhanced in fetal liver mitochondria by in utero ethanol exposure. Hepatology 1997;25:142–147.
   PubMed Web of Science ®Google Scholar
• Cohn JA, Tsai L, Friguet B, Szweda LI. Chemical characterization of a protein-4-hydroxy-2-nonenal cross-link: immunochemical detection in mitochondria exposed to oxidative stress. Arch Biochem Biophys 1996;328:158–164.
   PubMed Web of Science ®Google Scholar
• Liu W, Porter NA, Schneider C, Brash AR, Yin H. Formation of 4-hydroxynonenal from cardiolipin oxidation: intramolecular peroxyl radical addition and decomposition. Free Radic Biol Med 2011;50:166–178.
   PubMed Web of Science ®Google Scholar
• Dubinina EE, Dadali VA. Role of 4-hydroxy-trans-2-nonenal in cell functions. Biochemistry (Biokhimiia) 2010;75: 1069–1087.
   PubMed Web of Science ®Google Scholar
• Vasiliou V, Pappa A, Petersen DR. Role of aldehyde dehydrogenases in endogenous and xenobiotic metabolism. Chem Biol Interact 2000;129:1–19.
   PubMed Web of Science ®Google Scholar
• Marchitti SA, Brocker C, Stagos D, Vasiliou V. Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin Drug Metab Toxicol 2008;4:697–720.
   PubMed Web of Science ®Google Scholar
• Luckey SW, Petersen DR. Metabolism of 4-hydroxynonenal by rat Kupffer cells. Arch Biochem Biophys 2001;389:77–83.
   PubMed Web of Science ®Google Scholar
• Jackson B, Brocker C, Thompson DC, Black W, Vasiliou K, Nebert DW, Vasiliou V. Update on the aldehyde dehydrogenase gene (ALDH) superfamily. Human Genomics 2011;5: 283–303.
   PubMedGoogle Scholar
• Ma H, Guo R, Yu L, Zhang Y, Ren J. Aldehyde dehydrogenase 2 (ALDH2) rescues myocardial ischaemia/reperfusion injury: role of autophagy paradox and toxic aldehyde. Eur Heart J 2011;32:1025–1038.
   PubMed Web of Science ®Google Scholar
• Palaniyandi SS, Disatnik MH, Sun L, Vishnumangalam JJ, Xia X, Pavlovic A, et al. Aldehyde dehydrogenase activator attenuates diabetic cardiomyopathy; a role in improving the quality of resident cardiac stem cells?. Experimental Biology Meeting: FASEB J 2010;24 (MEETING ABSTRACT SUPPLEMENTS) 572. 3.
   Google Scholar
• Wang J, Wang H, Hao P, Xue L, Wei S, Zhang Y, Chen Y. Inhibition of aldehyde dehydrogenase 2 by oxidative stress is associated with cardiac dysfunction in diabetic rats. Mol Med 2011;17:172–179.
   PubMed Web of Science ®Google Scholar
• Hamblin M, Friedman DB, Hill S, Caprioli RM, Smith HM, Hill MF. Alterations in the diabetic myocardial proteome coupled with increased myocardial oxidative stress underlies diabetic cardiomyopathy. J Mol Cell Cardiol 2007;42:884–895.
   PubMed Web of Science ®Google Scholar
• Chen CH, Budas GR, Churchill EN, Disatnik MH, Hurley TD, Mochly-Rosen D. Activation of aldehyde dehydrogenase-2 reduces ischemic damage to the heart. Science 2008;321: 1493–1495.
   PubMed Web of Science ®Google Scholar
• Balogh LM, Atkins WM. Interactions of glutathione transferases with 4-hydroxynonenal. Drug Metab Rev 2011;43: 165–178.
   PubMed Web of Science ®Google Scholar
• Sharma R, Yang Y, Sharma A, Awasthi S, Awasthi YC. Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis. Antioxid Redox Signal 2004;6:289–300.
   PubMed Web of Science ®Google Scholar
• Srivastava S, Chandra A, Wang LF, Seifert WE Jr, DaGue BB, Ansari NH, et al. Metabolism of the lipid peroxidation product, 4-hydroxy-trans-2-nonenal, in isolated perfused rat heart. J Biol Chem 1998;273:10893–10900.
   PubMed Web of Science ®Google Scholar
• Ishikawa T, Esterbauer H, Sies H. Role of cardiac glutathione transferase and of the glutathione S-conjugate export system in biotransformation of 4-hydroxynonenal in the heart. J Biol Chem 1986;261:1576–1581.
   PubMed Web of Science ®Google Scholar
• Li Y, Cao Z, Zhu H, Trush MA. Differential roles of 3H-1,2-dithiole-3-thione-induced glutathione, glutathione S-transferase and aldose reductase in protecting against 4-hydroxy-2-nonenal toxicity in cultured cardiomyocytes. Arch Biochem Biophys 2005;439:80–90.
   PubMed Web of Science ®Google Scholar
• Srivastava S, Watowich SJ, Petrash JM, Srivastava SK, Bhatnagar A. Structural and kinetic determinants of aldehyde reduction by aldose reductase. Biochemistry 1999;38:42–54.
   PubMed Web of Science ®Google Scholar
• Shinmura K, Bolli R, Liu SQ, Tang XL, Kodani E, Xuan YT, et al. Aldose reductase is an obligatory mediator of the late phase of ischemic preconditioning. Circ Res 2002;91:240–246.
   PubMed Web of Science ®Google Scholar
• Rittner HL, Hafner V, Klimiuk PA, Szweda LI, Goronzy JJ, Weyand CM. Aldose reductase functions as a detoxification system for lipid peroxidation products in vasculitis. J Clin Invest 1999;103:1007–1013.
   PubMed Web of Science ®Google Scholar
• Kaiserova K, Tang XL, Srivastava S, Bhatnagar A. Role of nitric oxide in regulating aldose reductase activation in the ischemic heart. J Biol Chem 2008;283:9101–9112.
   PubMed Web of Science ®Google Scholar
• Srivastava S, Chandra A, Ansari NH, Srivastava SK, Bhatnagar A. Identification of cardiac oxidoreductase(s) involved in the metabolism of the lipid peroxidation-derived aldehyde-4-hydroxynonenal. Biochem J 1998;329:469–475.
   PubMed Web of Science ®Google Scholar
• Kaiserova K, Srivastava S, Hoetker JD, Awe SO, Tang XL, Cai J, Bhatnagar A. Redox activation of aldose reductase in the ischemic heart. J Biol Chem 2006;281:15110–15120.
   PubMed Web of Science ®Google Scholar
• Renner A, Sagstetter MR, Harms H, Lange V, Gotz ME, Elert O. Formation of 4-hydroxy-2-nonenal protein adducts in the ischemic rat heart after transplantation. J Heart Lung Transplant 2005;24:730–736.
   PubMed Web of Science ®Google Scholar
• Chen J, Henderson GI, Freeman GL. Role of 4-hydroxynonenal in modification of cytochrome c oxidase in ischemia/reperfused rat heart. J Mol Cell Cardiol 2001; 33:1919–1927.
   PubMed Web of Science ®Google Scholar
• Calabrese V, Mancuso C, Sapienza M, Puleo E, Calafato S, Cornelius C, et al. Oxidative stress and cellular stress response in diabetic nephropathy. Cell Stress Chaperones 2007;12:299–306.
   PubMed Web of Science ®Google Scholar
• Uchida K, Toyokuni S, Nishikawa K, Kawakishi S, Oda H, Hiai H, Stadtman ER. Michael addition-type 4-hydroxy-2-nonenal adducts in modified low-density lipoproteins: markers for atherosclerosis. Biochemistry 1994;33:12487–12494.
   PubMed Web of Science ®Google Scholar
• Wakita C, Honda K, Shibata T, Akagawa M, Uchida K. A method for detection of 4-hydroxy-2-nonenal adducts in proteins. Free Radic Biol Med 2011;51:1–4.
   PubMed Web of Science ®Google Scholar
• Carini M, Aldini G, Facino RM. Mass spectrometry for detection of 4-hydroxy-trans-2-nonenal (HNE) adducts with peptides and proteins. Mass Spectrom Rev 2004;23:281–305.
   PubMed Web of Science ®Google Scholar
• Eaton P, Li JM, Hearse DJ, Shattock MJ. Formation of 4-hydroxy-2-nonenal-modified proteins in ischemic rat heart. Am J Physiol 1999;276:H935–H943.
   PubMed Web of Science ®Google Scholar
• Leonarduzzi G, Chiarpotto E, Biasi F, Poli G. 4-Hydroxynonenal and cholesterol oxidation products in atherosclerosis. Mol Nutr Food Res 2005;49:1044–1049.
   PubMed Web of Science ®Google Scholar
• Pedersen WA, Fu W, Keller JN, Markesbery WR, Appel S, Smith RG, et al. Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients. Ann Neurol 1998;44: 819–824.
   PubMed Web of Science ®Google Scholar
• Zhang X, Wang Z, Li J, Gu D, Li S, Shen C, Song Z. Increased 4-hydroxynonenal formation contributes to obesity-related lipolytic activation in adipocytes. PloS one 2013; 8:e70663.
   Web of Science ®Google Scholar
• Lashin OM, Szweda PA, Szweda LI, Romani AM. Decreased complex II respiration and HNE-modified SDH subunit in diabetic heart. Free Radic Biol Med 2006;40:886–896.
   PubMed Web of Science ®Google Scholar
• Guo JM, Liu AJ, Zang P, Dong WZ, Ying L, Wang W, et al. ALDH2 protects against stroke by clearing 4-HNE. Cell Res 2013;23:915–930.
   PubMed Web of Science ®Google Scholar
• Lee WC, Wong HY, Chai YY, Shi CW, Amino N, Kikuchi S, Huang SH. Lipid peroxidation dysregulation in ischemic stroke: plasma 4-HNE as a potential biomarker?Biochem Biophys Res Commun 2012;425:842–847.
   PubMed Web of Science ®Google Scholar
• Pipinos II, Judge AR, Zhu Z, Selsby JT, Swanson SA, Johanning JM, et al. Mitochondrial defects and oxidative damage in patients with peripheral arterial disease. Free Radic Biol Med 2006;41:262–269.
   PubMed Web of Science ®Google Scholar
• Weiss DJ, Casale GP, Koutakis P, Nella AA, Swanson SA, Zhu Z, et al. Oxidative damage and myofiber degeneration in the gastrocnemius of patients with peripheral arterial disease. J Transl Med 2013;11:230.
   PubMed Web of Science ®Google Scholar
• Osaki K, Suzuki Y, Sugaya T, Tanifuji C, Nishiyama A, Horikoshi S, Tomino Y. Amelioration of angiotensin II- induced salt-sensitive hypertension by liver-type fatty acid-binding protein in proximal tubules. Hypertension 2013; 62:712–718.
   PubMedGoogle Scholar
• Chapple SJ, Cheng X, Mann GE. Effects of 4-hydroxynonenal on vascular endothelial and smooth muscle cell redox signaling and function in health and disease. Redox Biol 2013;1: 319–331.
   PubMed Web of Science ®Google Scholar
• Ruef J, Moser M, Bode C, Kubler W, Runge MS. 4-hydroxynonenal induces apoptosis, NF-kappaB-activation and formation of 8-isoprostane in vascular smooth muscle cells. Basic Res Cardiol 2001;96:143–150.
   PubMed Web of Science ®Google Scholar
• Napoli C, D’Armiento FP, Mancini FP, Postiglione A, Witztum JL, Palumbo G, Palinski W. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest 1997;100:2680–2690.
   PubMed Web of Science ®Google Scholar
• Pope AJ, Druhan L, Guzman JE, Forbes SP, Murugesan V, Lu D, et al. Role of DDAH-1 in lipid peroxidation product-mediated inhibition of endothelial NO generation. Am J Physiol Cell Physiol 2007;293:C1679–1686.
   PubMed Web of Science ®Google Scholar
• Selley ML, Bartlett MR, Czeti AL, Ardlie NG. The role of (E)-4-hydroxy-2-nonenal in platelet activation by low density lipoprotein and iron. Atherosclerosis 1998;140:105–112.
   PubMed Web of Science ®Google Scholar
• Yuan XM, Anders WL, Olsson AG, Brunk UT. Iron in human atheroma and LDL oxidation by macrophages following erythrophagocytosis. Atherosclerosis 1996;124:61–73.
   PubMed Web of Science ®Google Scholar
• Lee SJ, Seo KW, Yun MR, Bae SS, Lee WS, Hong KW, et al. 4-Hydroxynonenal enhances MMP-2 production in vascular smooth muscle cells via mitochondrial ROS-mediated activation of the Akt/NF-kappaB signaling pathways. Free Radic Biol Med 2008;45:1487–1492.
   PubMed Web of Science ®Google Scholar
• Forbes SP, Druhan LJ, Guzman JE, Parinandi N, Zhang L, Green-Church KB, Cardounel AJ. Mechanism of 4-HNE mediated inhibition of hDDAH-1: implications in no regulation. Biochemistry 2008;47:1819–1826.
   PubMed Web of Science ®Google Scholar
• Lu Z, Xu X, Hu X, Lee S, Traverse JH, Zhu G, et al. Oxidative stress regulates left ventricular PDE5 expression in the failing heart. Circulation 2010;121:1474–1483.
   PubMed Web of Science ®Google Scholar
• Coirault C, Guellich A, Barbry T, Samuel JL, Riou B, Lecarpentier Y. Oxidative stress of myosin contributes to skeletal muscle dysfunction in rats with chronic heart failure. Am J Physiol Heart Circ Physiol 2007;292:H1009–H1017.
   PubMed Web of Science ®Google Scholar
• Renes J, de Vries EE, Hooiveld GJ, Krikken I, Jansen PL, Muller M. Multidrug resistance protein MRP1 protects against the toxicity of the major lipid peroxidation product 4-hydroxynonenal. Biochem J 2000;350:555–561.
   PubMed Web of Science ®Google Scholar
• Zhang X, Li SY, Brown RA, Ren J. Ethanol and acetaldehyde in alcoholic cardiomyopathy: from bad to ugly en route to oxidative stress. Alcohol 2004;32:175–186.
   PubMed Web of Science ®Google Scholar
• Ren J, Wold LE. Mechanisms of alcoholic heart disease. Ther Adv Cardiovasc Dis 2008;2:497–506.
   PubMedGoogle Scholar
• Zhang Y, Ren J. ALDH2 in alcoholic heart diseases: molecular mechanism and clinical implications. Pharmacol Ther 2011;132:86–95.
   PubMed Web of Science ®Google Scholar
• Li SY, Ren J. Cardiac overexpression of alcohol dehydrogenase exacerbates chronic ethanol ingestion-induced myocardial dysfunction and hypertrophy: role of insulin signaling and ER stress. J Mol Cell Cardiol 2008;44:992–1001.
   PubMed Web of Science ®Google Scholar
• Ge W, Guo R, Ren J. AMP-dependent kinase and autophagic flux are involved in aldehyde dehydrogenase-2-induced protection against cardiac toxicity of ethanol. Free Radic Biol Med 2011;51:1736–1748.
   PubMed Web of Science ®Google Scholar
• Doser TA, Turdi S, Thomas DP, Epstein PN, Li SY, Ren J. Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction. Circulation 2009;119:1941–1949.
   PubMed Web of Science ®Google Scholar
• Mali VR, Ning R, Chen J, Xu J, Yang XP, Palaniyandi SS. Impairment of aldehyde dehydrogenase-2 by 4-hydroxy-2-nonenal adduct formation and cardiomyocyte hypertrophy in mice fed a high-fat diet and injected with low-dose streptozotocin (Experimental Biology and Medicine, in press).
   Google Scholar
• Traverso N, Menini S, Odetti P, Pronzato MA, Cottalasso D, Marinari UM. Diabetes impairs the enzymatic disposal of 4-hydroxynonenal in rat liver. Free Radic Biol Med 2002;32: 350–359.
   PubMed Web of Science ®Google Scholar
• Haenen GR, Plug HJ, Vermeulen NP, Timmerman H, Bast A. Contribution of 4-hydroxy-2,3-trans-nonenal to the reduction of beta-adrenoceptor function in the heart by oxidative stress. Life Sci 1989;45:71–76.
   PubMed Web of Science ®Google Scholar
• Lucas DT, Szweda LI. Cardiac reperfusion injury: aging, lipid peroxidation, and mitochondrial dysfunction. Proc Natl Acad Sci U S Am 1998;95:510–514.
   PubMed Web of Science ®Google Scholar
• Hill BG, Awe SO, Vladykovskaya E, Ahmed Y, Liu SQ, Bhatnagar A, Srivastava S. Myocardial ischaemia inhibits mitochondrial metabolism of 4-hydroxy-trans-2-nonenal. Biochem J 2009;417:513–524.
   PubMed Web of Science ®Google Scholar
• Bhatnagar A. Electrophysiological effects of 4-hydroxynonenal, an aldehydic product of lipid peroxidation, on isolated rat ventricular myocytes. Circ Res 1995;76:293–304.
   PubMed Web of Science ®Google Scholar
• Koda K, Salazar-Rodriguez M, Corti F, Chan NY, Estephan R, Silver RB, et al. Aldehyde dehydrogenase activation prevents reperfusion arrhythmias by inhibiting local renin release from cardiac mast cells. Circulation 2010;122: 771–781.
   PubMed Web of Science ®Google Scholar
• Yang Y, Sharma R, Sharma A, Awasthi S, Awasthi YC. Lipid peroxidation and cell cycle signaling: 4-hydroxynonenal, a key molecule in stress mediated signaling. Acta Biochim Pol 2003;50:319–336.
   PubMed Web of Science ®Google Scholar
• Chen ZH, Niki E. 4-hydroxynonenal (4-HNE) has been widely accepted as an inducer of oxidative stress. Is this the whole truth about it or can 4-HNE also exert protective effects?IUBMB Life. 2006;58:372–373.
   PubMed Web of Science ®Google Scholar
• Tai C, Zhu S, Zhou N. TRPA1: the central molecule for chemical sensing in pain pathway?J Neurosci 2008;28:1019–1021.
   PubMed Web of Science ®Google Scholar
• Trevisani M, Siemens J, Materazzi S, Bautista DM, Nassini R, Campi B, et al. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A 2007;104:13519–13524.
   PubMed Web of Science ®Google Scholar
• van der Kraaij AM, de Jonge HR, Esterbauer H, de Vente J, Steinbusch HW, Koster JF. Cumene hydroperoxide, an agent inducing lipid peroxidation, and 4-hydroxy-2,3-nonenal, a peroxidation product, cause coronary vasodilatation in perfused rat hearts by a cyclic nucleotide independent mechanism. Cardiovasc Res 1990;24:144–150.
   PubMed Web of Science ®Google Scholar
• Martinez MC, Bosch-Morell F, Raya A, Roma J, Aldasoro M, Vila J, et al. 4-Hydroxynonenal, a lipid peroxidation product, induces relaxation of human cerebral arteries. J Cereb Blood Flow Metab 1994;14:693–696.
   PubMed Web of Science ®Google Scholar
• Romero FJ, Romero MJ, Bosch-Morell F, Martinez MC, Medina P, Lluch S. 4-hydroxynonenal-induced relaxation of human mesenteric arteries. Free Radic Biol Med 1997;23: 521–523.
   PubMed Web of Science ®Google Scholar
• Dwivedi S, Sharma A, Patrick B, Sharma R, Awasthi YC. Role of 4-hydroxynonenal and its metabolites in signaling. Redox Rep 2007;12:4–10.
   PubMed Web of Science ®Google Scholar
• Dianzani MU. 4-hydroxynonenal from pathology to physiology. Mol Aspects Med 2003;24:263–272.
   PubMedGoogle Scholar
• Feng Z, Hu W, Tang MS. Trans-4-hydroxy-2-nonenal inhibits nucleotide excision repair in human cells: a possible mechanism for lipid peroxidation-induced carcinogenesis. Proc Natl Acad Sci U S A 2004;101:8598–8602.
   PubMed Web of Science ®Google Scholar
• Humphries KM, Szweda LI. Selective inactivation of alpha-ketoglutarate dehydrogenase and pyruvate dehydrogenase: reaction of lipoic acid with 4-hydroxy-2-nonenal. Biochemistry 1998;37:15835–15841.
   PubMed Web of Science ®Google Scholar
• Kristal BS, Park BK, Yu BP. 4-Hydroxyhexenal is a potent inducer of the mitochondrial permeability transition. J Biol Chem 1996;271:6033–6038.
   PubMed Web of Science ®Google Scholar
• Hill BG, Dranka BP, Zou L, Chatham JC, Darley-Usmar VM. Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal. Biochem J 2009;424:99–107.
   PubMed Web of Science ®Google Scholar
• Chen J, Robinson NC, Schenker S, Frosto TA, Henderson GI. Formation of 4-hydroxynonenal adducts with cytochrome c oxidase in rats following short-term ethanol intake. Hepatology 1999;29:1792–1798.
   PubMed Web of Science ®Google Scholar
• Patel VB, Spencer CH, Young TA, Lively MO, Cunningham CC. Effects of 4-hydroxynonenal on mitochondrial 3-hydroxy-3-methylglutaryl (HMG-CoA) synthase. Free Radic Biol Med 2007;43:1499–1507.
   PubMed Web of Science ®Google Scholar
• Benderdour M, Charron G, DeBlois D, Comte B, Des Rosiers C. Cardiac mitochondrial NADP+-isocitrate dehydrogenase is inactivated through 4-hydroxynonenal adduct formation: an event that precedes hypertrophy development. J Biol Chem 2003;278:45154–45159.
   PubMed Web of Science ®Google Scholar
• Ott M, Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria, oxidative stress and cell death. Apoptosis 2007;12:913–922.
   PubMed Web of Science ®Google Scholar
• Liu W, Kato M, Akhand AA, Hayakawa A, Suzuki H, Miyata T, et al. 4-hydroxynonenal induces a cellular redox status-related activation of the caspase cascade for apoptotic cell death. J Cell Sci 2000;113:635–641.
   PubMed Web of Science ®Google Scholar
• Ji C, Amarnath V, Pietenpol JA, Marnett LJ. 4-hydroxynonenal induces apoptosis via caspase-3 activation and cytochrome c release. Chem Res Toxicol 2001;14: 1090–1096.
   PubMed Web of Science ®Google Scholar
• Singh SP, Niemczyk M, Saini D, Awasthi YC, Zimniak L, Zimniak P. Role of the electrophilic lipid peroxidation product 4-hydroxynonenal in the development and maintenance of obesity in mice. Biochemistry 2008;47:3900–3911.
   PubMed Web of Science ®Google Scholar
• Grimsrud PA, Picklo MJ Sr, Griffin TJ, Bernlohr DA. Carbonylation of adipose proteins in obesity and insulin resistance: identification of adipocyte fatty acid-binding protein as a cellular target of 4-hydroxynonenal. Mol Cell Proteomics 2007;6:624–637.
   PubMed Web of Science ®Google Scholar
• Song BJ, Soh Y, Bae M, Pie J, Wan J, Jeong K. 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 2001;130–132:943–954.
   PubMed Web of Science ®Google Scholar
• Parola M, Robino G, Marra F, Pinzani M, Bellomo G, Leonarduzzi G, et al. HNE interacts directly with JNK isoforms in human hepatic stellate cells. J Clin Invest 1998;102:1942–1950.
   PubMed Web of Science ®Google Scholar
• Soh Y, Jeong KS, Lee IJ, Bae MA, Kim YC, Song BJ. Selective activation of the c-Jun N-terminal protein kinase pathway during 4-hydroxynonenal-induced apoptosis of PC12 cells. Mol Pharmacol 2000;58:535–541.
   PubMed Web of Science ®Google Scholar
• Takimoto T, Yoshida M, Hirata H, Suzuki M, Yanagita M, Kashiwa Y, et al. 4-hydroxy-2-nonenal induces endothelial cell injury via PKCδ and biphasic JNK activation. EXCLI J 2008;7:71–78.
   Web of Science ®Google Scholar
• McClung JM, Judge AR, Powers SK, Yan Z. p38 MAPK links oxidative stress to autophagy-related gene expression in cachectic muscle wasting. Am J Physiol Cell Physiol 2010;298:C542–549.
   PubMed Web of Science ®Google Scholar
• Usatyuk PV, Parinandi NL, Natarajan V. Redox regulation of 4-hydroxy-2-nonenal-mediated endothelial barrier dysfunction by focal adhesion, adherens, and tight junction proteins. J Biol Chem 2006;281:35554–35566.
   PubMed Web of Science ®Google Scholar
• Aberle NS II, Picklo MJ Sr, Amarnath V, Ren J. Inhibition of cardiac myocyte contraction by 4-hydroxy-trans-2-nonenal. Cardiovasc Toxicol 2004;4:21–28.
   PubMedGoogle Scholar
• Nakamura K, Miura D, Kusano KF, Fujimoto Y, Sumita-Yoshikawa W, Fuke S, et al. 4-Hydroxy-2-nonenal induces calcium overload via the generation of reactive oxygen species in isolated rat cardiac myocytes. J Card Fail 2009;15:709–716.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ren J. Autophagy in ALDH2-elicited cardioprotection against ischemic heart disease: slayer or savior?Autophagy 2010;6:1212–1213.
   PubMed Web of Science ®Google Scholar
• VanWinkle WB, Snuggs M, Miller JC, Buja LM. Cytoskeletal alterations in cultured cardiomyocytes following exposure to the lipid peroxidation product, 4-hydroxynonenal. Cell Motil Cytoskeleton 1994;28:119–134.
   PubMed Web of Science ®Google Scholar
• Miyata T, Kurokawa K. A detective story for biomedical footprints towards new therapeutic interventions in diabetic nephropathy. Intern Med 2003;42:1165–1171.
   PubMed Web of Science ®Google Scholar
• Korytar P, Molnarova M, Sivonova M, Zitnanova I, Ulicna O, Liptakova A, et al. Effects of aminoguanidine Schiff's base on biomarkers of the oxidative stress, 4-hydroxy-2-nonenal and conjugated dienes, in the model diabetes mellitus. Gen Physiol Biophys 2002;21:337–344.
   PubMed Web of Science ®Google Scholar
• Burcham PC, Kerr PG, Fontaine F. The antihypertensive hydralazine is an efficient scavenger of acrolein. Redox Rep 2000;5:47–49.
   PubMed Web of Science ®Google Scholar
• Galvani S, Coatrieux C, Elbaz M, Grazide MH, Thiers JC, Parini A, et al. Carbonyl scavenger and antiatherogenic effects of hydrazine derivatives. Free Radic Biol Med 2008;45:1457–1467.
   PubMed Web of Science ®Google Scholar
• Onorato JM, Jenkins AJ, Thorpe SR, Baynes JW. Pyridoxamine, an inhibitor of advanced glycation reactions, also inhibits advanced lipoxidation reactions. Mechanism of action of pyridoxamine. J Biol Chem 2000;275:21177–21184.
   PubMed Web of Science ®Google Scholar
• Miyata T, Ueda Y, Asahi K, Izuhara Y, Inagi R, Saito A, et al. Mechanism of the inhibitory effect of OPB-9195 [(+/−)-2-isopropylidenehydrazono-4-oxo-thiazolidin-5-yla cetanilide] on advanced glycation end product and advanced lipoxidation end product formation. J Am Soc Nephrol 2000;11:1719–1725.
   PubMed Web of Science ®Google Scholar
• Miyata T, van Ypersele de Strihou C, Ueda Y, Ichimori K, Inagi R, Onogi H, et al. Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: biochemical mechanisms. J Am Soc Nephrol 2002;13:2478–2487.
   PubMed Web of Science ®Google Scholar
• Davignon J, Jacob RF, Mason RP. The antioxidant effects of statins. Coron Artery Dis 2004;15:251–258.
   PubMed Web of Science ®Google Scholar
• Campos JC, Queliconi BB, Dourado PM, Cunha TF, Zambelli VO, Bechara LR, et al. Exercise training restores cardiac protein quality control in heart failure. PloS One 2012;7:e52764.
   PubMed Web of Science ®Google Scholar
• Morris RT, Laye MJ, Lees SJ, Rector RS, Thyfault JP, Booth FW. Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat. J Appl Physiol (1985). 2008;104: 708–715.
   PubMed Web of Science ®Google Scholar