The Disposal of Reactive Carbonyl Species through Carnosine Conjugation: What We Know Now

Author(s): Ettore Gilardoni, Giovanna Baron, Alessandra Altomare, Marina Carini, Giancarlo Aldini, Luca Regazzoni*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 11 , 2020


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Abstract:

Reactive Carbonyl Species are electrophiles generated by the oxidative cleavage of lipids and sugars. Such compounds have been described as important molecules for cellular signaling, whilst their accumulation has been found to be cytotoxic as they may trigger aberrant modifications of proteins (a process often referred to as carbonylation).

A correlation between carbonylation of proteins and human disease progression has been shown in ageing, diabetes, obesity, chronic renal failure, neurodegeneration and cardiovascular disease. However, the fate of reactive carbonyl species is still far from being understood, especially concerning the mechanisms responsible for their disposal as well as the importance of this in disease progression.

In this context, some data have been published on phase I and phase II deactivation of reactive carbonyl species. In the case of phase II mechanisms, the route involving glutathione conjugation and subsequent disposal of the adducts has been extensively studied both in vitro and in vivo for some of the more representative compounds, e.g. 4-hydroxynonenal.

There is also emerging evidence of an involvement of carnosine as an endogenous alternative to glutathione for phase II conjugation. However, the fate of carnosine conjugates is still poorly investigated and, unlike glutathione, there is little evidence of the formation of carnosine adducts in vivo. The acquisition of such data could be of importance for the development of new drugs, since carnosine and its derivatives have been proposed as potential therapeutic agents for the mitigation of carbonylation associated with disease progression.

Herein, we wish to review our current knowledge of the binding of reactive carbonyl species with carnosine together with the disposal of carnosine conjugates, emphasizing those aspects still requiring investigation such as conjugation reversibility and enzyme assisted catalysis of the reactions.

Keywords: Reactive carbonyl species, neurodegeneration, carnosine conjugates, trigger aberrant, glutathione, disease.

[1]
Reis, A.; Spickett, C.M. Chemistry of phospholipid oxidation. Biochim. Biophys. Acta, 2012, 1818(10), 2374-2387.
[http://dx.doi.org/10.1016/j.bbamem.2012.02.002] [PMID: 22342938]
[2]
Mano, J. Reactive carbonyl species: their production from lipid peroxides, action in environmental stress, and the detoxification mechanism. Plant Physiol. Biochem., 2012, 59, 90-97.
[http://dx.doi.org/10.1016/j.plaphy.2012.03.010] [PMID: 22578669]
[3]
Vistoli, G.; De Maddis, D.; Cipak, A.; Zarkovic, N.; Carini, M.; Aldini, G. Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation. Free Radic. Res., 2013, 47(Suppl. 1), 3-27.
[http://dx.doi.org/10.3109/10715762.2013.815348] [PMID: 23767955]
[4]
Cohen, G.; Riahi, Y.; Sunda, V.; Deplano, S.; Chatgilialoglu, C.; Ferreri, C.; Kaiser, N.; Sasson, S. Signaling properties of 4-hydroxyalkenals formed by lipid peroxidation in diabetes. Free Radic. Biol. Med., 2013, 65, 978-987.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.08.163] [PMID: 23973638]
[5]
Semchyshyn, H.M. Reactive carbonyl species in vivo: generation and dual biological effects. ScientificWorldJournal, 2014, 2014417842
[http://dx.doi.org/10.1155/2014/417842] [PMID: 24634611]
[6]
Pamplona, R. Advanced lipoxidation end-products. Chem. Biol. Interact., 2011, 192(1-2), 14-20.
[http://dx.doi.org/10.1016/j.cbi.2011.01.007] [PMID: 21238437]
[7]
Ayala, A.; Muñoz, M.F.; Argüelles, S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid. Med. Cell. Longev., 2014, 2014360438
[http://dx.doi.org/10.1155/2014/360438] [PMID: 24999379]
[8]
Falletti, O.; Cadet, J.; Favier, A.; Douki, T. Trapping of 4-hydroxynonenal by glutathione efficiently prevents formation of DNA adducts in human cells. Free Radic. Biol. Med., 2007, 42(8), 1258-1269.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.01.024] [PMID: 17382206]
[9]
Dubinina, E.E.; Dadali, V.A. Role of 4-hydroxy-trans-2-nonenal in cell functions. Biochemistry (Mosc.), 2010, 75(9), 1069-1087.
[http://dx.doi.org/10.1134/S0006297910090014] [PMID: 21077827]
[10]
Lyons, T.J.; Jenkins, A.J. Glycation, oxidation, and lipoxidation in the development of the complications of diabetes: a carbonyl stress hypothesis. Diabetes Rev. (Alex.), 1997, 5(4), 365-391.
[PMID: 26366051]
[11]
Suzuki, D.; Miyata, T.; Kurokawa, K. Carbonyl stress. Contrib. Nephrol., 2001, (134), 36-45.
[http://dx.doi.org/10.1159/000060151] [PMID: 11665286]
[12]
Miyata, T. Alterations of non-enzymatic biochemistry in uremia, diabetes, and atherosclerosis (“carbonyl stress”). Bull. Mem. Acad. R. Med. Belg., 2002, 157(3-4), 189-196.
[PMID: 12508715]
[13]
Cabiscol, E.; Tamarit, J.; Ros, J. Protein carbonylation: proteomics, specificity and relevance to aging. Mass Spectrom. Rev., 2014, 33(1), 21-48.
[http://dx.doi.org/10.1002/mas.21375] [PMID: 24114980]
[14]
Ruskovska, T.; Bernlohr, D.A. Oxidative stress and protein carbonylation in adipose tissue - implications for insulin resistance and diabetes mellitus. J. Proteomics, 2013, 92, 323-334.
[http://dx.doi.org/10.1016/j.jprot.2013.04.002] [PMID: 23584148]
[15]
Bollineni, R.C.; Fedorova, M.; Blüher, M.; Hoffmann, R. Carbonylated plasma proteins as potential biomarkers of obesity induced type 2 diabetes mellitus. J. Proteome Res., 2014, 13(11), 5081-5093.
[http://dx.doi.org/10.1021/pr500324y] [PMID: 25010493]
[16]
Murdolo, G.; Piroddi, M.; Luchetti, F.; Tortoioli, C.; Canonico, B.; Zerbinati, C.; Galli, F.; Iuliano, L. Oxidative stress and lipid peroxidation by-products at the crossroad between adipose organ dysregulation and obesity-linked insulin resistance. Biochimie, 2013, 95(3), 585-594.
[http://dx.doi.org/10.1016/j.biochi.2012.12.014] [PMID: 23274128]
[17]
Tucker, P.S.; Dalbo, V.J.; Han, T.; Kingsley, M.I. Clinical and research markers of oxidative stress in chronic kidney disease. Biomarkers, 2013, 18(2), 103-115.
[http://dx.doi.org/10.3109/1354750X.2012.749302] [PMID: 23339563]
[18]
Wang, P.; Xie, K.; Wang, C.; Bi, J. Oxidative stress induced by lipid peroxidation is related with inflammation of demyelination and neurodegeneration in multiple sclerosis. Eur. Neurol., 2014, 72(3-4), 249-254.
[http://dx.doi.org/10.1159/000363515] [PMID: 25277682]
[19]
Sultana, R.; Perluigi, M.; Butterfield, D.A. Lipid peroxidation triggers neurodegeneration: a redox proteomics view into the Alzheimer disease brain. Free Radic. Biol. Med., 2013, 62, 157-169.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.09.027] [PMID: 23044265]
[20]
Zhang, P.Y.; Xu, X.; Li, X.C. Cardiovascular diseases: oxidative damage and antioxidant protection. Eur. Rev. Med. Pharmacol. Sci., 2014, 18(20), 3091-3096.
[PMID: 25392110]
[21]
Dalle-Donne, I.; Giustarini, D.; Colombo, R.; Rossi, R.; Milzani, A. Protein carbonylation in human diseases. Trends Mol. Med., 2003, 9(4), 169-176.
[http://dx.doi.org/10.1016/S1471-4914(03)00031-5] [PMID: 12727143]
[22]
Levine, R.L. Carbonyl modified proteins in cellular regulation, aging, and disease. Free Radic. Biol. Med., 2002, 32(9), 790-796.
[http://dx.doi.org/10.1016/S0891-5849(02)00765-7] [PMID: 11978480]
[23]
Mol, M.; Regazzoni, L.; Altomare, A.; Degani, G.; Carini, M.; Vistoli, G.; Aldini, G. Enzymatic and non-enzymatic detoxification of 4-hydroxynonenal: Methodological aspects and biological consequences. Free Radic. Biol. Med., 2017, 111, 328-344.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.01.036] [PMID: 28161307]
[24]
Parent, R.A.; Paust, D.E.; Schrimpf, M.K.; Talaat, R.E.; Doane, R.A.; Caravello, H.E.; Lee, S.J.; Sharp, D.E. Metabolism and distribution of [2,3-14C]acrolein in Sprague-Dawley rats. II. Identification of urinary and fecal metabolites. Toxicol. Sci., 1998, 43(2), 110-120.
[http://dx.doi.org/10.1006/toxs.1998.2462] [PMID: 9710952]
[25]
Carini, M.; Aldini, G.; Beretta, G.; Arlandini, E.; Facino, R.M. Acrolein-sequestering ability of endogenous dipeptides: characterization of carnosine and homocarnosine/acrolein adducts by electrospray ionization tandem mass spectrometry. J. Mass Spectrom., 2003, 38(9), 996-1006.
[http://dx.doi.org/10.1002/jms.517] [PMID: 14505328]
[26]
Aldini, G.; Carini, M.; Beretta, G.; Bradamante, S.; Facino, R.M. Carnosine is a quencher of 4-hydroxy-nonenal: through what mechanism of reaction? Biochem. Biophys. Res. Commun., 2002, 298(5), 699-706.
[http://dx.doi.org/10.1016/S0006-291X(02)02545-7] [PMID: 12419310]
[27]
Aldini, G.; Dalle-Donne, I.; Colombo, R.; Maffei Facino, R.; Milzani, A.; Carini, M. Lipoxidation-derived reactive carbonyl species as potential drug targets in preventing protein carbonylation and related cellular dysfunction. ChemMedChem, 2006, 1(10), 1045-1058.
[http://dx.doi.org/10.1002/cmdc.200600075] [PMID: 16915603]
[28]
Song, B.C.; Joo, N.S.; Aldini, G.; Yeum, K.J. Biological functions of histidine-dipeptides and metabolic syndrome. Nutr. Res. Pract., 2014, 8(1), 3-10.
[http://dx.doi.org/10.4162/nrp.2014.8.1.3] [PMID: 24611099]
[29]
Hoetker, D.; Chung, W.; Zhang, D.; Zhao, J.; Schmidtke, V.K.; Riggs, D.W.; Derave, W.; Bhatnagar, A.; Bishop, D.J.; Baba, S.P. Exercise alters and β-alanine combined with exercise augments histidyl dipeptide levels and scavenges lipid peroxidation products in human skeletal muscle. J.Appl. Physiol., 2018, 1985.
[30]
Carvalho, V.H.; Oliveira, A.H.S.; de Oliveira, L.F.; da Silva, R.P.; Di Mascio, P.; Gualano, B.; Artioli, G.G.; Medeiros, M.H.G. Exercise and β-alanine supplementation on carnosine-acrolein adduct in skeletal muscle. Redox Biol., 2018, 18, 222-228.
[http://dx.doi.org/10.1016/j.redox.2018.07.009] [PMID: 30053728]
[31]
Aldini, G.; Orioli, M.; Rossoni, G.; Savi, F.; Braidotti, P.; Vistoli, G.; Yeum, K.J.; Negrisoli, G.; Carini, M. The carbonyl scavenger carnosine ameliorates dyslipidaemia and renal function in Zucker obese rats. J. Cell. Mol. Med., 2011, 15(6), 1339-1354.
[http://dx.doi.org/10.1111/j.1582-4934.2010.01101.x] [PMID: 20518851]
[32]
Albrecht, T.; Schilperoort, M.; Zhang, S.; Braun, J.D.; Qiu, J.; Rodriguez, A.; Pastene, D.O.; Krämer, B.K.; Köppel, H.; Baelde, H.; de Heer, E.; Anna Altomare, A.; Regazzoni, L.; Denisi, A.; Aldini, G.; van den Born, J.; Yard, B.A.; Hauske, S.J. Carnosine attenuates the development of both Type 2 Diabetes and diabetic nephropathy in BTBR ob/ob Mice. Sci. Rep., 2017, 7, 44492.
[http://dx.doi.org/10.1038/srep44492] [PMID: 28281693]
[33]
Dobrotvorskaya, I.S.; Fedorova, T.N.; Dobrota, D.; Berezov, T.T. Characteristics of oxidative stress in experimental rat brain ischemia aggravated by homocysteic acid. Neurochem. J., 2011, 5(1), 42-46.
[http://dx.doi.org/10.1134/S1819712410041014]
[34]
Bae, O.N.; Serfozo, K.; Baek, S.H.; Lee, K.Y.; Dorrance, A.; Rumbeiha, W.; Fitzgerald, S.D.; Farooq, M.U.; Naravelta, B.; Bhatt, A.; Majid, A. Safety and efficacy evaluation of carnosine, an endogenous neuroprotective agent for ischemic stroke. Stroke, 2013, 44(1), 205-212.
[http://dx.doi.org/10.1161/STROKEAHA.112.673954] [PMID: 23250994]
[35]
Renner, C.; Zemitzsch, N.; Fuchs, B.; Geiger, K.D.; Hermes, M.; Hengstler, J.; Gebhardt, R.; Meixensberger, J.; Gaunitz, F. Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model. Mol. Cancer, 2010, 9, 2.
[http://dx.doi.org/10.1186/1476-4598-9-2] [PMID: 20053283]
[36]
Tsai, S.J.; Kuo, W.W.; Liu, W.H.; Yin, M.C. Antioxidative and anti-inflammatory protection from carnosine in the striatum of MPTP-treated mice. J. Agric. Food Chem., 2010, 58(21), 11510-11516.
[http://dx.doi.org/10.1021/jf103258p] [PMID: 20925384]
[37]
Herculano, B.; Tamura, M.; Ohba, A.; Shimatani, M.; Kutsuna, N.; Hisatsune, T. β-alanyl-L-histidine rescues cognitive deficits caused by feeding a high fat diet in a transgenic mouse model of Alzheimer’s disease. J. Alzheimers Dis., 2013, 33(4), 983-997.
[http://dx.doi.org/10.3233/JAD-2012-121324] [PMID: 23099816]
[38]
Barski, O.A.; Xie, Z.; Baba, S.P.; Sithu, S.D.; Agarwal, A.; Cai, J.; Bhatnagar, A.; Srivastava, S. Dietary carnosine prevents early atherosclerotic lesion formation in apolipoprotein E-null mice. Arterioscler. Thromb. Vasc. Biol., 2013, 33(6), 1162-1170.
[http://dx.doi.org/10.1161/ATVBAHA.112.300572] [PMID: 23559625]
[39]
Baye, E.; Ukropec, J.; de Courten, M.P.; Vallova, S.; Krumpolec, P.; Kurdiova, T.; Aldini, G.; Ukropcova, B.; de Courten, B. Effect of carnosine supplementation on the plasma lipidome in overweight and obese adults: a pilot randomised controlled trial. Sci. Rep., 2017, 7(1), 17458.
[http://dx.doi.org/10.1038/s41598-017-17577-7] [PMID: 29234057]
[40]
Regazzoni, L.; de Courten, B.; Garzon, D.; Altomare, A.; Marinello, C.; Jakubova, M.; Vallova, S.; Krumpolec, P.; Carini, M.; Ukropec, J.; Ukropcova, B.; Aldini, G. A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect. Sci. Rep., 2016, 6, 27224.
[http://dx.doi.org/10.1038/srep27224] [PMID: 27265207]
[41]
de Courten, B.; Jakubova, M.; de Courten, M.P.; Kukurova, I.J.; Vallova, S.; Krumpolec, P.; Valkovic, L.; Kurdiova, T.; Garzon, D.; Barbaresi, S.; Teede, H.J.; Derave, W.; Krssak, M.; Aldini, G.; Ukropec, J.; Ukropcova, B. Effects of carnosine supplementation on glucose metabolism: Pilot clinical trial. Obesity (Silver Spring), 2016, 24(5), 1027-1034.
[http://dx.doi.org/10.1002/oby.21434] [PMID: 27040154]
[42]
Doorn, J.A.; Petersen, D.R. Covalent modification of amino acid nucleophiles by the lipid peroxidation products 4-hydroxy-2-nonenal and 4-oxo-2-nonenal. Chem. Res. Toxicol., 2002, 15(11), 1445-1450.
[http://dx.doi.org/10.1021/tx025590o] [PMID: 12437335]
[43]
Colzani, M.; De Maddis, D.; Casali, G.; Carini, M.; Vistoli, G.; Aldini, G. Reactivity, selectivity, and reaction mechanisms of aminoguanidine, hydralazine, pyridoxamine, and carnosine as sequestering agents of reactive carbonyl species: a comparative study. ChemMedChem, 2016, 11(16), 1778-1789.
[http://dx.doi.org/10.1002/cmdc.201500552] [PMID: 26891408]
[44]
Alin, P.; Danielson, U.H.; Mannervik, B. 4-Hydroxyalk-2-enals are substrates for glutathione transferase. FEBS Lett., 1985, 179(2), 267-270.
[http://dx.doi.org/10.1016/0014-5793(85)80532-9] [PMID: 3838159]
[45]
Berhane, K.; Mannervik, B. Inactivation of the genotoxic aldehyde acrolein by human glutathione transferases of classes alpha, mu, and pi. Mol. Pharmacol., 1990, 37(2), 251-254.
[PMID: 2304453]
[46]
Baba, S.P.; Hoetker, J.D.; Merchant, M.; Klein, J.B.; Cai, J.; Barski, O.A.; Conklin, D.J.; Bhatnagar, A. Role of aldose reductase in the metabolism and detoxification of carnosine-acrolein conjugates. J. Biol. Chem., 2013, 288(39), 28163-28179.
[http://dx.doi.org/10.1074/jbc.M113.504753] [PMID: 23928303]
[47]
Aldini, G.; Vistoli, G.; Regazzoni, L.; Gamberoni, L.; Facino, R.M.; Yamaguchi, S.; Uchida, K.; Carini, M. Albumin is the main nucleophilic target of human plasma: a protective role against pro-atherogenic electrophilic reactive carbonyl species? Chem. Res. Toxicol., 2008, 21(4), 824-835.
[http://dx.doi.org/10.1021/tx700349r] [PMID: 18324789]
[48]
Turell, L.; Radi, R.; Alvarez, B. The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic. Biol. Med., 2013, 65, 244-253.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.05.050] [PMID: 23747983]
[49]
Li, Q.; Tomcik, K.; Zhang, S.; Puchowicz, M.A.; Zhang, G.F. Dietary regulation of catabolic disposal of 4-hydroxynonenal analogs in rat liver. Free Radic. Biol. Med., 2012, 52(6), 1043-1053.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.12.022] [PMID: 22245097]
[50]
Mannion, A.F.; Jakeman, P.M.; Dunnett, M.; Harris, R.C.; Willan, P.L. Carnosine and anserine concentrations in the quadriceps femoris muscle of healthy humans. Eur. J. Appl. Physiol. Occup. Physiol., 1992, 64(1), 47-50.
[http://dx.doi.org/10.1007/BF00376439] [PMID: 1735411]
[51]
Aldini, G.; Granata, P.; Carini, M. Detoxification of cytotoxic alpha,beta-unsaturated aldehydes by carnosine: characterization of conjugated adducts by electrospray ionization tandem mass spectrometry and detection by liquid chromatography/mass spectrometry in rat skeletal muscle. J. Mass Spectrom., 2002, 37(12), 1219-1228.
[http://dx.doi.org/10.1002/jms.381] [PMID: 12489081]
[52]
Alary, J.; Fernandez, Y.; Debrauwer, L.; Perdu, E.; Guéraud, F. Identification of intermediate pathways of 4-hydroxynonenal metabolism in the rat. Chem. Res. Toxicol., 2003, 16(3), 320-327.
[http://dx.doi.org/10.1021/tx025671k] [PMID: 12641432]
[53]
Uchida, K. 4-Hydroxy-2-nonenal: a product and mediator of oxidative stress. Prog. Lipid Res., 2003, 42(4), 318-343.
[http://dx.doi.org/10.1016/S0163-7827(03)00014-6] [PMID: 12689622]
[54]
Dillard, C.J.; Litov, R.E.; Savin, W.M.; Dumelin, E.E.; Tappel, A.L. Effects of exercise, vitamin E, and ozone on pulmonary function and lipid peroxidation. J. Appl. Physiol., 1978, 45(6), 927-932.
[http://dx.doi.org/10.1152/jappl.1978.45.6.927] [PMID: 730598]
[55]
Quindry, J.; Dumke, C.; Slivka, D.; Ruby, B. Impact of extreme exercise at high altitude on oxidative stress in humans. J. Physiol., 2016, 594(18), 5093-5104.
[http://dx.doi.org/10.1113/JP270651] [PMID: 26453842]
[56]
Elokda, A.S.; Nielsen, D.H. Effects of exercise training on the glutathione antioxidant system. Eur. J. Cardiovasc. Prev. Rehabil., 2007, 14(5), 630-637.
[http://dx.doi.org/10.1097/HJR.0b013e32828622d7] [PMID: 17925621]
[57]
Atalay, M.; Seene, T.; Hänninen, O.; Sen, C.K. Skeletal muscle and heart antioxidant defences in response to sprint training. Acta Physiol. Scand., 1996, 158(2), 129-134.
[http://dx.doi.org/10.1046/j.1365-201X.1996.540305000.x] [PMID: 8899059]
[58]
Sen, C.K.; Marin, E.; Kretzschmar, M.; Hanninen, O. keletal muscle and liver glutathione homeostasis in response to training, exercise, and immobilization. J Appl Physiol (1985), , 1992, 73(4), 1265-1272.
[59]
Powers, S.K.; Ji, L.L.; Leeuwenburgh, C. Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. Med. Sci. Sports Exerc., 1999, 31(7), 987-997.
[http://dx.doi.org/10.1097/00005768-199907000-00011] [PMID: 10416560]
[60]
Brownson, C.; Hipkiss, A.R. Carnosine reacts with a glycated protein. Free Radic. Biol. Med., 2000, 28(10), 1564-1570.
[http://dx.doi.org/10.1016/S0891-5849(00)00270-7] [PMID: 10927182]
[61]
Hipkiss, A.R.; Brownson, C.; Bertani, M.F.; Ruiz, E.; Ferro, A. Reaction of carnosine with aged proteins: another protective process? Ann. N. Y. Acad. Sci., 2002, 959, 285-294.
[http://dx.doi.org/10.1111/j.1749-6632.2002.tb02100.x] [PMID: 11976203]
[62]
Hipkiss, A.R.; Chana, H. Carnosine protects proteins against methylglyoxal-mediated modifications. Biochem. Biophys. Res. Commun., 1998, 248(1), 28-32.
[http://dx.doi.org/10.1006/bbrc.1998.8806] [PMID: 9675080]
[63]
Cai, J.; Bhatnagar, A.; Pierce, W.M., Jr Protein modification by acrolein: formation and stability of cysteine adducts. Chem. Res. Toxicol., 2009, 22(4), 708-716.
[http://dx.doi.org/10.1021/tx800465m] [PMID: 19231900]
[64]
Ponist, S.; Drafi, F.; Kuncirova, V.; Mihalova, D.; Rackova, L.; Danisovic, L.; Ondrejickova, O.; Tumova, I.; Trunova, O.; Fedorova, T.; Bauerova, K. Effect of carnosine in experimental arthritis and on primary culture chondrocytes. Oxid. Med. Cell. Longev., 2016, 20168470589
[http://dx.doi.org/10.1155/2016/8470589] [PMID: 26885252]
[65]
Menini, S.; Iacobini, C.; Ricci, C.; Scipioni, A.; Blasetti Fantauzzi, C.; Giaccari, A.; Salomone, E.; Canevotti, R.; Lapolla, A.; Orioli, M.; Aldini, G.; Pugliese, G. D-Carnosine octylester attenuates atherosclerosis and renal disease in ApoE null mice fed a Western diet through reduction of carbonyl stress and inflammation. Br. J. Pharmacol., 2012, 166(4), 1344-1356.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01834.x] [PMID: 22229552]
[66]
Hipkiss, A.R.; Brownson, C. Carnosine reacts with protein carbonyl groups: another possible role for the anti-ageing peptide? Biogerontology, 2000, 1(3), 217-223.
[http://dx.doi.org/10.1023/A:1010057412184] [PMID: 11707898]
[67]
Srivastava, S.; Chandra, A.; Bhatnagar, A.; Srivastava, S.K.; Ansari, N.H. Lipid peroxidation product, 4-hydroxynonenal and its conjugate with GSH are excellent substrates of bovine lens aldose reductase. Biochem. Biophys. Res. Commun., 1995, 217(3), 741-746.
[http://dx.doi.org/10.1006/bbrc.1995.2835] [PMID: 8554593]
[68]
Rotondo, R.; Moschini, R.; Renzone, G.; Tuccinardi, T.; Balestri, F.; Cappiello, M.; Scaloni, A.; Mura, U.; Del-Corso, A. Human carbonyl reductase 1 as efficient catalyst for the reduction of glutathionylated aldehydes derived from lipid peroxidation. Free Radic. Biol. Med., 2016, 99, 323-332.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.08.015] [PMID: 27562619]
[69]
Hartley, D.P.; Ruth, J.A.; Petersen, D.R. The hepatocellular metabolism of 4-hydroxynonenal by alcohol dehydrogenase, aldehyde dehydrogenase, and glutathione S-transferase. Arch. Biochem. Biophys., 1995, 316(1), 197-205.
[http://dx.doi.org/10.1006/abbi.1995.1028] [PMID: 7840616]
[70]
Stevens, J.F.; Maier, C.S. Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol. Nutr. Food Res., 2008, 52(1), 7-25.
[http://dx.doi.org/10.1002/mnfr.200700412] [PMID: 18203133]
[71]
Ramana, K.V.; Dixit, B.L.; Srivastava, S.; Balendiran, G.K.; Srivastava, S.K.; Bhatnagar, A. Selective recognition of glutathiolated aldehydes by aldose reductase. Biochemistry, 2000, 39(40), 12172-12180.
[http://dx.doi.org/10.1021/bi000796e] [PMID: 11015195]
[72]
Peters, V.; Jansen, E.E.; Jakobs, C.; Riedl, E.; Janssen, B.; Yard, B.A.; Wedel, J.; Hoffmann, G.F.; Zschocke, J.; Gotthardt, D.; Fischer, C.; Köppel, H. Anserine inhibits carnosine degradation but in human serum carnosinase (CN1) is not correlated with histidine dipeptide concentration. Clin. Chim. Acta, 2011, 412(3-4), 263-267.
[http://dx.doi.org/10.1016/j.cca.2010.10.016] [PMID: 20971102]
[73]
Peters, V.; Lanthaler, B.; Amberger, A.; Fleming, T.; Forsberg, E.; Hecker, M.; Wagner, A.H.; Yue, W.W.; Hoffmann, G.F.; Nawroth, P.; Zschocke, J.; Schmitt, C.P. Carnosine metabolism in diabetes is altered by reactive metabolites. Amino Acids, 2015, 47(11), 2367-2376.
[http://dx.doi.org/10.1007/s00726-015-2024-z] [PMID: 26081982]
[74]
Orioli, M.; Aldini, G.; Benfatto, M.C.; Facino, R.M.; Carini, M. HNE Michael adducts to histidine and histidine-containing peptides as biomarkers of lipid-derived carbonyl stress in urines: LC-MS/MS profiling in Zucker obese rats. Anal. Chem., 2007, 79(23), 9174-9184.
[http://dx.doi.org/10.1021/ac7016184] [PMID: 17979257]
[75]
Aldini, G.; Granata, P.; Orioli, M.; Santaniello, E.; Carini, M. Detoxification of 4-hydroxynonenal (HNE) in keratinocytes: characterization of conjugated metabolites by liquid chromatography/electrospray ionization tandem mass spectrometry. J. Mass Spectrom., 2003, 38(11), 1160-1168.
[http://dx.doi.org/10.1002/jms.533] [PMID: 14648823]
[76]
Keller, J.; Baradat, M.; Jouanin, I.; Debrauwer, L.; Guéraud, F. “Twin peaks”: searching for 4-hydroxynonenal urinary metabolites after oral administration in rats. Redox Biol., 2015, 4, 136-148.
[http://dx.doi.org/10.1016/j.redox.2014.12.016] [PMID: 25560242]
[77]
Bauchart, C.; Savary-Auzeloux, I.; Patureau Mirand, P.; Thomas, E.; Morzel, M.; Rémond, D. Carnosine concentration of ingested meat affects carnosine net release into the portal vein of minipigs. J. Nutr., 2007, 137(3), 589-593.
[http://dx.doi.org/10.1093/jn/137.3.589] [PMID: 17311945]
[78]
Kamal, M.A.; Jiang, H.; Hu, Y.; Keep, R.F.; Smith, D.E. Influence of genetic knockout of Pept2 on the in vivo disposition of endogenous and exogenous carnosine in wild-type and Pept2 null mice. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2009, 296(4), R986-R991.
[http://dx.doi.org/10.1152/ajpregu.90744.2008] [PMID: 19225147]
[79]
Yamashita, T.; Shimada, S.; Guo, W.; Sato, K.; Kohmura, E.; Hayakawa, T.; Takagi, T.; Tohyama, M. Cloning and functional expression of a brain peptide/histidine transporter. J. Biol. Chem., 1997, 272(15), 10205-10211.
[http://dx.doi.org/10.1074/jbc.272.15.10205] [PMID: 9092568]
[80]
Bastecký, J.; Cervenka, J. Proceedings: Nonspecific reactions of the FPN Forrest test. Act. Nerv. Super. (Praha), 1975, 17(4), 305-306.
[PMID: 1221811]
[81]
Teufel, M.; Saudek, V.; Ledig, J.P.; Bernhardt, A.; Boularand, S.; Carreau, A.; Cairns, N.J.; Carter, C.; Cowley, D.J.; Duverger, D.; Ganzhorn, A.J.; Guenet, C.; Heintzelmann, B.; Laucher, V.; Sauvage, C.; Smirnova, T. Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. J. Biol. Chem., 2003, 278(8), 6521-6531.
[http://dx.doi.org/10.1074/jbc.M209764200] [PMID: 12473676]
[82]
Usui, T. Kubo, Y.; Akanuma, S.; Hosoya, K. Β-alanine and l-histidine transport across the inner blood-retinal barrier: potential involvement in L-carnosine supply. Exp. Eye Res., 2013, 113, 135-142.
[http://dx.doi.org/10.1016/j.exer.2013.06.002] [PMID: 23773890]
[83]
Liu, W.; Liang, R.; Ramamoorthy, S.; Fei, Y.J.; Ganapathy, M.E.; Hediger, M.A.; Ganapathy, V.; Leibach, F.H. Molecular cloning of PEPT 2, a new member of the H+/peptide cotransporter family, from human kidney. Biochim. Biophys. Acta, 1995, 1235(2), 461-466.
[http://dx.doi.org/10.1016/0005-2736(95)80036-F] [PMID: 7756356]
[84]
Botka, C.W.; Wittig, T.W.; Graul, R.C.; Nielsen, C.U.; Higaka, K.; Amidon, G.L.; Sadée, W. Human proton/oligopeptide transporter (POT) genes: identification of putative human genes using bioinformatics. AAPS PharmSci, 2000, 2(2)E16
[http://dx.doi.org/10.1208/ps020216] [PMID: 11741232]
[85]
Herrera-Ruiz, D.; Wang, Q.; Gudmundsson, O.S.; Cook, T.J.; Smith, R.L.; Faria, T.N.; Knipp, G.T. Spatial expression patterns of peptide transporters in the human and rat gastrointestinal tracts, Caco-2 in vitro cell culture model, and multiple human tissues. AAPS PharmSci, 2001, 3(1), E9.
[http://dx.doi.org/10.1208/ps030109] [PMID: 11741260]
[86]
Bhardwaj, R.K.; Herrera-Ruiz, D.; Eltoukhy, N.; Saad, M.; Knipp, G.T. The functional evaluation of human peptide/histidine transporter 1 (hPHT1) in transiently transfected COS-7 cells. Eur. J. Pharm. Sci., 2006, 27(5), 533-542.
[http://dx.doi.org/10.1016/j.ejps.2005.09.014] [PMID: 16289537]
[87]
Jhiang, S.M.; Fithian, L.; Smanik, P.; McGill, J.; Tong, Q.; Mazzaferri, E.L. Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells. FEBS Lett., 1993, 318(2), 139-144.
[http://dx.doi.org/10.1016/0014-5793(93)80008-I] [PMID: 8382624]
[88]
Prasad, P.D.; Wang, H.; Huang, W.; Kekuda, R.; Rajan, D.P.; Leibach, F.H.; Ganapathy, V. Human LAT1, a subunit of system L amino acid transporter: molecular cloning and transport function. Biochem. Biophys. Res. Commun., 1999, 255(2), 283-288.
[http://dx.doi.org/10.1006/bbrc.1999.0206] [PMID: 10049700]
[89]
Tsurudome, M.; Ito, M.; Takebayashi, S.; Okumura, K.; Nishio, M.; Kawano, M.; Kusagawa, S.; Komada, H.; Ito, Y. Cutting edge: primary structure of the light chain of fusion regulatory protein-1/CD98/4F2 predicts a protein with multiple transmembrane domains that is almost identical to the amino acid transporter E16. J. Immunol., 1999, 162(5), 2462-2466.
[PMID: 10072483]
[90]
Yanagida, O.; Kanai, Y.; Chairoungdua, A.; Kim, D.K.; Segawa, H.; Nii, T.; Cha, S.H.; Matsuo, H.; Fukushima, J.; Fukasawa, Y.; Tani, Y.; Taketani, Y.; Uchino, H.; Kim, J.Y.; Inatomi, J.; Okayasu, I.; Miyamoto, K.; Takeda, E.; Goya, T.; Endou, H. Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim. Biophys. Acta, 2001, 1514(2), 291-302.
[http://dx.doi.org/10.1016/S0005-2736(01)00384-4] [PMID: 11557028]
[91]
Gaugitsch, H.W.; Prieschl, E.E.; Kalthoff, F.; Huber, N.E.; Baumruker, T. A novel transiently expressed, integral membrane protein linked to cell activation. Molecular cloning via the rapid degradation signal AUUUA. J. Biol. Chem., 1992, 267(16), 11267-11273.
[PMID: 1597461]
[92]
Ritchie, J.W.; Taylor, P.M. Role of the System L permease LAT1 in amino acid and iodothyronine transport in placenta. Biochem. J., 2001, 356(Pt 3), 719-725.
[http://dx.doi.org/10.1042/bj3560719] [PMID: 11389679]
[93]
Okamoto, Y.; Sakata, M.; Ogura, K.; Yamamoto, T.; Yamaguchi, M.; Tasaka, K.; Kurachi, H.; Tsurudome, M.; Murata, Y. Expression and regulation of 4F2hc and hLAT1 in human trophoblasts. Am. J. Physiol. Cell Physiol., 2002, 282(1), C196-C204.
[http://dx.doi.org/10.1152/ajpcell.2002.282.1.C196] [PMID: 11742812]
[94]
Jain-Vakkalagadda, B.; Dey, S.; Pal, D.; Mitra, A.K. Identification and functional characterization of a Na+-independent large neutral amino acid transporter, LAT1, in human and rabbit cornea. Invest. Ophthalmol. Vis. Sci., 2003, 44(7), 2919-2927.
[http://dx.doi.org/10.1167/iovs.02-0907] [PMID: 12824232]
[95]
Fraga, S.; Pinho, M.J.; Soares-da-Silva, P. Expression of LAT1 and LAT2 amino acid transporters in human and rat intestinal epithelial cells. Amino Acids, 2005, 29(3), 229-233.
[http://dx.doi.org/10.1007/s00726-005-0221-x] [PMID: 16027961]
[96]
Nawashiro, H.; Otani, N.; Shinomiya, N.; Fukui, S.; Ooigawa, H.; Shima, K.; Matsuo, H.; Kanai, Y.; Endou, H. L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. Int. J. Cancer, 2006, 119(3), 484-492.
[http://dx.doi.org/10.1002/ijc.21866] [PMID: 16496379]
[97]
Boldyrev, A.A.; Aldini, G.; Derave, W. Physiology and pathophysiology of carnosine. Physiol. Rev., 2013, 93(4), 1803-1845.
[http://dx.doi.org/10.1152/physrev.00039.2012] [PMID: 24137022]
[98]
Drozak, J.; Veiga-da-Cunha, M.; Vertommen, D.; Stroobant, V.; Van Schaftingen, E. Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). J. Biol. Chem., 2010, 285(13), 9346-9356.
[http://dx.doi.org/10.1074/jbc.M109.095505] [PMID: 20097752]
[99]
Yeum, K.J.; Orioli, M.; Regazzoni, L.; Carini, M.; Rasmussen, H.; Russell, R.M.; Aldini, G. Profiling histidine dipeptides in plasma and urine after ingesting beef, chicken or chicken broth in humans. Amino Acids, 2010, 38(3), 847-858.
[http://dx.doi.org/10.1007/s00726-009-0291-2] [PMID: 19381778]
[100]
Gardner, M.L.; Illingworth, K.M.; Kelleher, J.; Wood, D. Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose. J. Physiol., 1991, 439, 411-422.
[http://dx.doi.org/10.1113/jphysiol.1991.sp018673] [PMID: 1910085]
[101]
Watzek, N.; Scherbl, D.; Feld, J.; Berger, F.; Doroshyenko, O.; Fuhr, U.; Tomalik-Scharte, D.; Baum, M.; Eisenbrand, G.; Richling, E. Profiling of mercapturic acids of acrolein and acrylamide in human urine after consumption of potato crisps. Mol. Nutr. Food Res., 2012, 56(12), 1825-1837.
[http://dx.doi.org/10.1002/mnfr.201200323] [PMID: 23109489]
[102]
Abraham, K.; Andres, S.; Palavinskas, R.; Berg, K.; Appel, K.E.; Lampen, A. Toxicology and risk assessment of acrolein in food. Mol. Nutr. Food Res., 2011, 55(9), 1277-1290.
[http://dx.doi.org/10.1002/mnfr.201100481] [PMID: 21898908]
[103]
Csallany, A.S.; Han, I.; Shoeman, D.W.; Chen, C.; Yuan, J.Y. 4-hydroxynonenal (HNE), a toxic aldehyde in french fries from fast food restaurants. J. Am. Oil Chem. Soc., 2015, 92(10), 1413-1419.
[http://dx.doi.org/10.1007/s11746-015-2699-z]
[104]
Sakai, T.; Kuwazuru, S.; Yamauchi, K.; Uchida, K. A lipid peroxidation-derived aldehyde, 4-hydroxy-2-nonenal and omega 6 fatty acids contents in meats. Biosci. Biotechnol. Biochem., 1995, 59(7), 1379-1380.
[http://dx.doi.org/10.1271/bbb.59.1379] [PMID: 7670203]
[105]
Gasc, N.; Taché, S.; Rathahao, E.; Bertrand-Michel, J.; Roques, V.; Guéraud, F. 4-hydroxynonenal in foodstuffs: heme concentration, fatty acid composition and freeze-drying are determining factors. Redox Rep., 2007, 12(1), 40-44.
[http://dx.doi.org/10.1179/135100007X162257] [PMID: 17263907]
[106]
Laurent, A.; Alary, J.; Debrauwer, L.; Cravedi, J.P. Analysis in the rat of 4-hydroxynonenal metabolites excreted in bile: evidence of enterohepatic circulation of these byproducts of lipid peroxidation. Chem. Res. Toxicol., 1999, 12(10), 887-894.
[http://dx.doi.org/10.1021/tx9900425] [PMID: 10525263]
[107]
Dygas, A.; Makowski, P.; Pikuła, S. Is the glutathione conjugate of trans-4-hydroxy-2-nonenal transported by the multispecific organic anion transporting-ATPase of human erythrocytes? Acta Biochim. Pol., 1998, 45(1), 59-65.
[http://dx.doi.org/10.18388/abp.1998_4318] [PMID: 9701496]
[108]
Singhal, S.S.; Yadav, S.; Roth, C.; Singhal, J. RLIP76: A novel glutathione-conjugate and multi-drug transporter. Biochem. Pharmacol., 2009, 77(5), 761-769.
[http://dx.doi.org/10.1016/j.bcp.2008.10.006] [PMID: 18983828]
[109]
Enoiu, M.; Herber, R.; Wennig, R.; Marson, C.; Bodaud, H.; Leroy, P.; Mitrea, N.; Siest, G.; Wellman, M. gamma-Glutamyltranspeptidase-dependent metabolism of 4-hydroxynonenal-glutathione conjugate. Arch. Biochem. Biophys., 2002, 397(1), 18-27.
[http://dx.doi.org/10.1006/abbi.2001.2633] [PMID: 11747306]
[110]
Aldini, G.; Facino, R.M.; Beretta, G.; Carini, M. Carnosine and related dipeptides as quenchers of reactive carbonyl species: from structural studies to therapeutic perspectives. Biofactors, 2005, 24(1-4), 77-87.
[http://dx.doi.org/10.1002/biof.5520240109] [PMID: 16403966]
[111]
Babizhayev, M.A.; Yermakova, V.N.; Sakina, N.L.; Evstigneeva, R.P.; Rozhkova, E.A.; Zheltukhina, G.A. N alpha-acetylcarnosine is a prodrug of L-carnosine in ophthalmic application as antioxidant. Clin. Chim. Acta, 1996, 254(1), 1-21.
[http://dx.doi.org/10.1016/0009-8981(96)06356-5] [PMID: 8894306]
[112]
Petras, T.; Siems, W.G.; Grune, T. 4-hydroxynonenal is degraded to mercapturic acid conjugate in rat kidney. Free Radic. Biol. Med., 1995, 19(5), 685-688.
[http://dx.doi.org/10.1016/0891-5849(95)00060-B] [PMID: 8529929]
[113]
Hinchman, C.A.; Ballatori, N. Glutathione conjugation and conversion to mercapturic acids can occur as an intrahepatic process. J. Toxicol. Environ. Health, 1994, 41(4), 387-409.
[http://dx.doi.org/10.1080/15287399409531852] [PMID: 8145281]
[114]
Bauer, K.; Schulz, M. Biosynthesis of carnosine and related peptides by skeletal muscle cells in primary culture. European journal of biochemistry / FEBS,, 1994, 219(1-2), 43-47.
[http://dx.doi.org/10.1111/j.1432-1033.1994.tb19912.x]
[115]
Drozak, J.; Piecuch, M.; Poleszak, O.; Kozlowski, P.; Chrobok, L.; Baelde, H.J.; de Heer, E. UPF0586 Protein C9orf41 homolog is anserine-producing methyltransferase. J. Biol. Chem., 2015, 290(28), 17190-17205.
[http://dx.doi.org/10.1074/jbc.M115.640037] [PMID: 26001783]
[116]
Peters, V.; Klessens, C.Q.; Baelde, H.J.; Singler, B.; Veraar, K.A.; Zutinic, A.; Drozak, J.; Zschocke, J.; Schmitt, C.P.; de Heer, E. Intrinsic carnosine metabolism in the human kidney. Amino Acids, 2015, 47(12), 2541-2550.
[http://dx.doi.org/10.1007/s00726-015-2045-7] [PMID: 26206726]
[117]
Nadkarni, D.V.; Sayre, L.M. Structural definition of early lysine and histidine adduction chemistry of 4-hydroxynonenal. Chem. Res. Toxicol., 1995, 8(2), 284-291.
[http://dx.doi.org/10.1021/tx00044a014] [PMID: 7766813]


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VOLUME: 27
ISSUE: 11
Year: 2020
Published on: 23 April, 2020
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DOI: 10.2174/0929867326666190624094813
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