Molecular mechanisms of acrolein toxicity: Relevance to human disease

Toxicological Sciences

Volumn 143, Issue 2, 2015, Pages 242-255

  Moghe, Akshata ^a   Ghare, Smita ^a   Lamoreau, Bryan ^a   Mohammad, Mohammad ^a   Barve, Shirish ^a   McClain, Craig ^a,b   Joshi Barve, Swati ^a  

^a University of Louisville School of Medicine   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Antioxidants; Apoptosis; DNA adducts; Environmental; Exposure; Inflammation; Oxidative injury

Indexed keywords

ACROLEIN; ALPHA TOCOPHEROL; ANTIOXIDANT; CYTOKINE; DNA ADDUCT; POLLUTANT;

ARTICLE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA DAMAGE; ENDOPLASMIC RETICULUM STRESS; HUMAN; IMMUNOPATHOLOGY; INFLAMMATION; METABOLISM; OXIDATIVE STRESS; SIGNAL TRANSDUCTION; TOXICITY; ADVERSE EFFECTS; APOPTOSIS; DISEASE; DNA ADDUCT; DRUG EFFECTS; ENVIRONMENTAL EXPOSURE; IMMUNOLOGY; MITOCHONDRION; POLLUTANT;

ACROLEIN; ANTIOXIDANTS; APOPTOSIS; CYTOKINES; DISEASE; DNA ADDUCTS; ENVIRONMENTAL EXPOSURE; ENVIRONMENTAL POLLUTANTS; HUMANS; MITOCHONDRIA; OXIDATIVE STRESS; SIGNAL TRANSDUCTION;

EID: 84924673274     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfu233     Document Type: Article

References (143)

1. Abraham, K., Andres, S., Palavinskas, R., Berg, K., Appel, K. E., and Lampen, A. (2011). Toxicology and risk assessment of acrolein in food. Mol. Nutr. Food Res. 55, 1277-1290.
2. Adams, J. D., Jr. and Klaidman, L. K. (1993). Acrolein-induced oxygen radical formation. Free Radic. Biol. Med. 15, 187-193.
3. Ahmed, M. S., Langer, H., Abed, M., Voelkl, J., and Lang, F. (2013). The uremic toxin acrolein promotes suicidal erythrocyte death. Kidney Blood Press. Res. 37, 158-167.
4. Alarcon, R. A. (2012). Anticancer system created by acrolein and hydroxyl radical generated in enzymatic oxidation of spermine and other biochemical reactions. Med. Hypotheses 79, 522-530.
5. Aldini, G., Orioli, M., and Carini, M. (2011). Protein modification by acrolein: relevance to pathological conditions and inhibition by aldehyde sequestering agents. Mol. Nutr. Food Res. 55, 1301-1319.
6. Avezov, K., Reznick, A. Z., and Aizenbud, D. (2014a). LDH enzyme activity in human saliva: the effect of exposure to cigarette smoke and its different components. Arch. Oral Biol. 59, 142-148.
7. Avezov, K., Reznick, A. Z., and Aizenbud, D. (2014b). Oxidative damage in keratinocytes exposed to cigarette smoke and aldehydes. Toxicol. in vitro 28, 485-491.
8. Beillerot, A., Battaglia, E., Aline, B., and Bagrel, D. (2012). Protection of CDC25 phosphatases against oxidative stress in breast cancer cells: evaluation of the implication of the thioredoxin system. Free Radic. Res. 46, 674-689.
9. Birben, E., Sahiner, U. M., Sackesen, C., Erzurum, S., and Kalayci, O. (2012). Oxidative stress and antioxidant defense. World Allergy Organ. J. 5, 9-19.
10. Brooks, W. H. (2013). Increased polyamines alter chromatin and stabilize autoantigens in autoimmune diseases. Front. Immunol. 4, 91.
11. Bui, L. C., Manaa, A., Xu, X., Duval, R., Busi, F., Dupret, J. M., Rodrigues Lima, F., and Dairou, J. (2013). Acrolein, an alpha, beta-unsaturated aldehyde, irreversibly inhibits the acetylation of aromatic amine xenobiotics by human Nat1. Drug Metab. Dispos. 41, 1300-1305.
12. Burcham, P. C., Raso, A., and Henry, P. J. (2014). Airborne acrolein induces keratin-8 (Ser-73) hyperphosphorylation and intermediate filament ubiquitination in bronchiolar lung cell monolayers. Toxicology 319, 44-52.
13. Burcham, P. C., Raso, A., and Kaminskas, L. M. (2012). Chaperone heat shock protein 90 mobilization and hydralazine cytoprotection against acrolein-induced carbonyl stress. Mol. Pharmacol. 82, 876-886.
14. Cahill, T. M. (2014). Ambient acrolein concentrations in coastal, remote, and urban regions in California. Environ. Sci. Technol. 48, 8507-8513.
15. Carbone, D. L., Doorn, J. A., Kiebler, Z., and Petersen, D. R. (2005). Cysteine modification by lipid peroxidation products inhibits protein disulfide isomerase. Chem. Res. Toxicol. 18, 1324-1331.
16. Centers for Disease, C., and Prevention (2013). Notes from the field: acute pesticide-related illness resulting from occupational exposure to acrolein - washington and california, 1993-2009. MMWR 62, 313-314.
17. Chen, Y. J., Chen, P., Wang, H. X., Wang, T., Chen, L., Wang, X., Sun, B. B., Liu, D. S., Xu, D., An, J., and Wen, F. Q. (2010). Simvastatin attenuates acrolein-induced mucin production in rats: involvement of the Ras/extracellular signal-regulated kinase pathway. Int. Immunopharmacol. 10, 685-693.
18. Chen, D., Fang, L., Li, H., Tang, M. S., and Jin, C. (2013). Cigarette smoke component acrolein modulates chromatin assembly by inhibiting histone acetylation. J. Biol. Chem. 288, 21678-21687.
19. Choudhury, S., Dyba, M., Pan, J., Roy, R., and Chung, F. L. (2013). Repair kinetics of acrolein- and (E)-4-hydroxy-2-nonenalderived DNA adducts in human colon cell extracts. Mutat. Res. 751-752, 15-23.
20. Cohen, S. M., Garland, E. M., St John, M., Okamura, T., and Smith, R. A. (1992). Acrolein initiates rat urinary bladder carcinogenesis. Cancer Res. 52, 3577-3581.
21. Colombo, G., Dalle-Donne, I., Orioli, M., Giustarini, D., Rossi, R., Clerici, M., Regazzoni, L., Aldini, G., Milzani, A., Butterfield, D. A., and Gagliano, N. (2012). Oxidative damage in human gingival fibroblasts exposed to cigarette smoke. Free Radic. Biol. Med. 52, 1584-1596.
22. Comer, D. M., Elborn, J. S., and Ennis, M. (2014). Inflammatory and cytotoxic effects of acrolein, nicotine, acetylaldehyde and cigarette smoke extract on human nasal epithelial cells. BMC Pulm. Med. 14, 32.
23. Conklin, D. J., Bhatnagar, A., Cowley, H. R., Johnson, G. H., Wiechmann, R. J., Sayre, L. M., Trent, M. B., and Boor, P. J. (2006). Acrolein generation stimulates hypercontraction in isolated human blood vessels. Toxicol. Appl. Pharmacol. 217, 277-288.
24. Cox, R., Goorha, S., and Irving, C. C. (1988). Inhibition of DNA methylase activity by acrolein. Carcinogenesis 9, 463-465.
25. Demir, E., Turna, F., Kaya, B., Creus, A., and Marcos, R. (2013). Mutagenic/recombinogenic effects of four lipid peroxidation products in Drosophila. Food Chem. Toxicol. 53, 221-227.
26. Deshmukh, H. S., Case, L. M., Wesselkamper, S. C., Borchers, M. T., Martin, L. D., Shertzer, H. G., Nadel, J. A., and Leikauf, G. D. (2005). Metalloproteinases mediate mucin 5AC expression by epidermal growth factor receptor activation. Am. J. Respir. Crit. Care Med. 171, 305-314.
27. Dong, L., Zhou, S., Yang, X., Chen, Q., He, Y., and Huang, W. (2013). Magnolol protects against oxidative stressmediated neural cell damage by modulating mitochondrial dysfunction and PI3K/Akt signaling. J. Mol. Neurosci. 50, 469-481.
28. Dorman, D. C., Struve, M. F., Wong, B. A., Marshall, M. W., Gross, E. A., and Willson, G. A. (2008). Respiratory tract responses in male rats following subchronic acrolein inhalation. Inhal. Toxicol. 20, 205-216.
29. Due, M. R., Park, J., Zheng, L., Walls, M., Allette, Y. M., White, F. A., and Shi, R. (2014). Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat. J. Neurochem. 128, 776-786.
30. Fathi, A. R., Krautheim, A., Kaap, S., Eger, K., and Steinfelder, H. J. (2000). Michael adducts of ascorbic acid as inhibitors of protein phosphatase 2A and inducers of apoptosis. Bioorg. Med. Chem. Lett. 10, 1605-1608.
31. Feng, Z., Hu, W., Hu, Y., and Tang, M. S. (2006). Acrolein is a major cigarette-related lung cancer agent: Preferential binding at p53 mutational hotspots and inhibition of DNA repair. Proc. Natl. Acad. Sci. U.S.A. 103, 15404-15409.
32. Feng, Z., Liu, Z., Li, X., Jia, H., Sun, L., Tian, C., Jia, L., and Liu, J. (2010). Alpha-tocopherol is an effective Phase II enzyme inducer: protective effects on acrolein-induced oxidative stress and mitochondrial dysfunction in human retinal pigment epithelial cells. J. Nutr. Biochem. 21, 1222-1231.
33. Finkelstein, E. I., Nardini, M., and Van der Vliet, A. (2001). Inhibition of neutrophil apoptosis by acrolein: a mechanism of tobacco-related lung disease?. Am. J. Physiol. Lung C 281, L732-L739.
34. Galligan, J. J., Smathers, R. L., Fritz, K. S., Epperson, L. E., Hunter, L. E., and Petersen, D. R. (2012). Protein carbonylation in a murine model for early alcoholic liver disease. Chem. Res. Toxicol. 25, 1012-1021.
35. Gan, G., Hu, R., Dai, A., Tan, S., Ouyang, Q., Fu, D., and Jiang, D. (2011). The role of endoplasmic reticulum stress in emphysema results from cigarette smoke exposure. Cell. Physiol. Biochem. 28, 725-732.
36. Grigsby, J., Betts, B., Vidro-Kotchan, E., Culbert, R., and Tsin, A. (2012). A possible role of acrolein in diabetic retinopathy: involvement of a VEGF/TGFbeta signaling pathway of the retinal pigment epithelium in hyperglycemia. Curr. Eye Res. 37, 1045-1053.
37. Haberzettl, P., Vladykovskaya, E., Srivastava, S., and Bhatnagar, A. (2009). Role of endoplasmic reticulum stress in acroleininduced endothelial activation. Toxicol. Appl. Pharmacol. 234, 14-24.
38. Hamann, K., Nehrt, G., Ouyang, H., Duerstock, B., and Shi, R. (2008). Hydralazine inhibits compression and acroleinmediated injuries in ex vivo spinal cord. J. Neurochem. 104, 708-718.
39. Hamann, K. and Shi, R. (2009). Acrolein scavenging: a potential novel mechanism of attenuating oxidative stress following spinal cord injury. J. Neurochem. 111, 1348-1356.
40. He, X., Song, W., Liu, C., Chen, S., and Hua, J. (2014). Rapamycin inhibits acrolein-induced apoptosis by alleviating ROSdriven mitochondrial dysfunction in male germ cells. Cell Prolif. 47, 161-171.
41. Hengstermann, A. and Muller, T. (2008). Endoplasmic reticulum stress induced by aqueous extracts of cigarette smoke in 3T3 cells activates the unfolded-protein-response-dependent PERK pathway of cell survival. Free Radic. Biol. Med. 44, 1097-1107.
42. Hochman, D. J., Collaco, C. R., and Brooks, E. G. (2014). Acrolein induction of oxidative stress and degranulation in mast cells. Environ. Toxicol. 29, 908-915.
43. Horton, N. D., Biswal, S. S., Corrigan, L. L., Bratta, J., and Kehrer, J. P. (1999). Acrolein causes inhibitor kappaB-independent decreases in nuclear factor kappaB activation in human lung adenocarcinoma (A549) cells. J. Biol. Chem. 274, 9200-9206.
44. Hristova, M., Heuvelmans, S., and van der Vliet, A. (2007). GSHdependent regulation of Fas-mediated caspase-8 activation by acrolein. Febs Lett. 581, 361-367.
45. Hristova, M., Spiess, P. C., Kasahara, D. I., Randall, M. J., Deng, B., and van der Vliet, A. (2012). The tobacco smoke component, acrolein, suppresses innate macrophage responses by direct alkylation of c-Jun N-terminal kinase. Am. J. Respir. Cell Mol. Biol. 46, 23-33.
46. Huang, Y., Qin, J., Chen, M., Chao, X., Chen, Z., Ramassamy, C., Pi, R., and Jin, M. (2014). Lithium prevents acrolein-induced neurotoxicity in HT22 mouse hippocampal cells. Neurochem. Res. 39, 677-684.
47. Igarashi, K. and Kashiwagi, K. (2011). Protein-conjugated acrolein as a biochemical marker of brain infarction. Mol. Nutr. Food Res. 55, 1332-1341.
48. Il'yasova, D., Scarbrough, P., and Spasojevic, I. (2012). Urinary biomarkers of oxidative status. Clin. Chim. Acta 413, 1446-1453.
49. Ismahil, M. A., Hamid, T., Haberzettl, P., Gu, Y., Chandrasekar, B., Srivastava, S., Bhatnagar, A., and Prabhu, S. D. (2011). Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy. Am. J. Physiol. Heart Circ. Physiol. 301, H2050-H2060.
50. Jeong, M. S. and Kang, J. H. (2008). Acrolein, the toxic endogenous aldehyde, induces neurofilament-L aggregation. BMB Rep. 41, 635-639.
51. Jia, L., Liu, Z., Sun, L., Miller, S. S., Ames, B. N., Cotman, C. W., and Liu, J. (2007). Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid. Invest. Ophthalmol. Vis. Sci. 48, 339-348.
52. Joshi-Barve, S., Amancherla, K., Patil, M., Bhatnagar, A., Mathews, S., Gobejishvili, L., Cave, M., McClain, C., and Barve, S. (2009). Acrolein, a ubiquitous pollutant and lipid hydroperoxide product, inhibits antiviral activity of interferon-alpha: relevance to hepatitis C. Free Radic. Biol. Med. 47, 47-54.
53. Kasahara, D. I., Poynter, M. E., Othman, Z., Hemenway, D., and van der Vliet, A. (2008). Acrolein inhalation suppresses lipopolysaccharide-induced inflammatory cytokine production but does not affect acute airways neutrophilia. J. Immunol. 181, 736-745.
54. Kasiviswanathan, R., Minko, I. G., Lloyd, R. S., and Copeland, W. C. (2013). Translesion synthesis past acrolein-derived DNA adducts by human mitochondrial DNA polymerase gamma. J. Biol. Chem. 288, 14247-14255.
55. Kassem, N. O., Daffa, R. M., Liles, S., Jackson, S. R., Kassem, N. O., Younis, M. A., Mehta, S., Chen, M., Jacob, P., 3rd, Carmella, S. G., et al. (2014). Children's exposure to secondhand and thirdhand smoke carcinogens and toxicants in homes of hookah smokers. Nicotine Tobacco Res. 16, 961-975.
56. Kawai, Y., Furuhata, A., Toyokuni, S., Aratani, Y., and Uchida, K. (2003). Formation of acrolein-derived 2'-deoxyadenosine adduct in an iron-induced carcinogenesis model. J. Biol. Chem. 278, 50346-50354.
57. Kehrer, J. P., and Biswal, S. S. (2000). The molecular effects of acrolein. Toxicol. Sci. 57, 6-15.
58. Keith, R. J., Haberzettl, P., Vladykovskaya, E., Hill, B. G., Kaiserova, K., Srivastava, S., Barski, O., and Bhatnagar, A. (2009). Aldose reductase decreases endoplasmic reticulum stress in ischemic hearts. Chem. Biol. Int. 178, 242-249.
59. Kern, J. C. and Kehrer, J. P. (2002). Acrolein-induced cell death: a caspase-influenced decision between apoptosis and oncosis/necrosis. Chem. Biol. Int. 139, 79-95.
60. Kim, S. H., Lee, I. C., Baek, H. S., Shin, I. S., Moon, C., Bae, C. S., Kim, S. H., Kim, J. C., and Kim, H. C. (2014). Mechanism for the protective effect of diallyl disulfide against cyclophosphamide acute urotoxicity in rats. Food Chem. Toxicol. 64, 110-118.
61. Kim, G. D., Lee, S. E., Kim, T. H., Jin, Y. H., Park, Y. S., and Park, C. S. (2012). Melatonin suppresses acrolein-induced IL-8 production in human pulmonary fibroblasts. J. Pineal Res. 52, 356-364.
62. Kim, C. E., Lee, S. J., Seo, K.W., Park, H.M., Yun, J.W., Bae, J. U., Bae, S. S., and Kim, C. D. (2010). Acrolein increases 5-lipoxygenase expression in murine macrophages through activation of ERK pathway. Toxicol. Appl. Pharmacol. 245, 76-82.
63. Kim, S. I., Pfeifer, G. P., and Besaratinia, A. (2007). Lack of mutagenicity of acrolein-induced DNA adducts in mouse and human cells. Cancer Res. 67, 11640-11647.
64. Kirkham, P. A., Spooner, G., Rahman, I., and Rossi, A. G. (2004). Macrophage phagocytosis of apoptotic neutrophils is compromised by matrix proteins modified by cigarette smoke and lipid peroxidation products. Biochem. Biophys. Res. Commun. 318, 32-37.
65. Kitaguchi, Y., Taraseviciene-Stewart, L., Hanaoka, M., Natarajan, R., Kraskauskas, D., and Voelkel, N. F. (2012). Acrolein induces endoplasmic reticulum stress and causes airspace enlargement. PloS One 7, e38038.
66. Korkmaz, A., Topal, T., and Oter, S. (2007). Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARP activation. Cell Biol. Toxicol. 23, 303-312.
67. Lambert, C., Li, J., Jonscher, K., Yang, T. C., Reigan, P., Quintana, M., Harvey, J., and Freed, B. M. (2007). Acrolein inhibits cytokine gene expression by alkylating cysteine and arginine residues in the NF-kappaB1 DNA binding domain. J. Biol. Chem. 282, 19666-19675.
68. Lambert, C., McCue, J., Portas, M., Ouyang, Y., Li, J., Rosano, T. G., Lazis, A., and Freed, B. M. (2005). Acrolein in cigarette smoke inhibits T-cell responses. J. Allergy Clin. Immunol. 116, 916-922.
69. Lee, H. W., Wang, H. T., Weng, M. W., Hu, Y., Chen, W. S., Chou, D., Liu, Y., Donin, N., Huang, W. C., Lepor, H., et al. (2014). Acrolein- and 4-aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells. Oncotarget 5, 3526-3540.
70. Leung, G., Sun, W., Zheng, L., Brookes, S., Tully, M., and Shi, R. (2011). Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in experimental autoimmune encephalomyelitis mouse. Neuroscience 173, 150-155.
71. Li, J. Q., Yu, J. T., Jiang, T., and Tan, L. (2014). Endoplasmic reticulum dysfunction in Alzheimer's Disease. Mol. Neurobiol. doi:10.1007/s12035-014-8695-8.
72. Liu, D. S., Liu, W. J., Chen, L., Ou, X. M., Wang, T., Feng, Y. L., Zhang, S. F., Xu, D., Chen, Y. J., and Wen, F. Q. (2009). Rosiglitazone, a peroxisome proliferator-activated receptorgamma agonist, attenuates acrolein-induced airway mucus hypersecretion in rats. Toxicology 260, 112-119.
73. Liu, F., Li, X. L., Lin, T., He, D. W., Wei, G. H., Liu, J. H., and Li, L. S. (2012). The cyclophosphamide metabolite, acrolein, induces cytoskeletal changes and oxidative stress in Sertoli cells. Mol. Biol. Rep. 39, 493-500.
74. Liu, X. Y., Zhu, M. X., and Xie, J. P. (2010). Mutagenicity of acrolein and acrolein-induced DNA adducts. Toxicol. Mech. Methods 20, 36-44.
75. Logue, J. M., Price, P. N., Sherman, M. H., and Singer, B. C. (2012). A method to estimate the chronic health impact of air pollutants in U.S. residences. Environ. Health Persp. 120, 216-222.
76. Lopachin, R. M., Barber, D. S., Geohagen, B. C., Gavin, T., He, D., and Das, S. (2007). Structure-toxicity analysis of type-2 alkenes: in vitro neurotoxicity. Toxicol. Sci. 95, 136-146.
77. Luo, J. and Shi, R. (2004). Acrolein induces axolemmal disruption, oxidative stress, and mitochondrial impairment in spinal cord tissue. Neurochem. Int. 44, 475-486.
78. MacAllister, S. L., Martin-Brisac, N., Lau, V., Yang, K., and O'Brien, P. J. (2013). Acrolein and chloroacetaldehyde: an examination of the cell and cell-free biomarkers of toxicity. Chem. Biol. Int. 202, 259-266.
79. Maczurek, A., Hager, K., Kenklies, M., Sharman, M., Martins, R., Engel, J., Carlson, D. A., and Munch, G. (2008). Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer's disease. Adv. Drug Deliv. Rev. 60, 1463-1470.
80. Maddox, J. F., Roth, R. A., and Ganey, P. E. (2003). Allyl alcohol activation of protein kinase C delta leads to cytotoxicity of rat hepatocytes. Chem. Res. Toxicol. 16, 609-615.
81. Martyniuk, C. J., Fang, B., Koomen, J. M., Gavin, T., Zhang, L., Barber, D. S., and Lopachin, R. M. (2011). Molecular mechanism of glyceraldehyde-3-phosphate dehydrogenase inactivation by alpha, beta-unsaturated carbonyl derivatives. Chem. Res. Toxicol. 24, 2302-2311.
82. Medina-Navarro, R., Nieto-Aguilar, R., and Alvares-Aguilar, C. (2011). Protein conjugated with aldehydes derived from lipid peroxidation as an independent parameter of the carbonyl stress in the kidney damage. Lipids Health Dis. 10, 201.
83. Mizoi, M., Yoshida, M., Saiki, R., Waragai, M., Uemura, K., Akatsu, H., Kashiwagi, K., and Igarashi, K. (2014). Distinction between mild cognitive impairment and Alzheimer's disease by CSF amyloid beta40 and beta42, and protein-conjugated acrolein. Clin. Chim. Acta 430, 150-155.
84. Mohammad, M. K., Avila, D., Zhang, J., Barve, S., Arteel, G., McClain, C., and Joshi-Barve, S. (2012). Acrolein cytotoxicity in hepatocytes involves endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress. Toxicol. Appl. Pharmacol. 265, 73-82.
85. Moretto, N., Bertolini, S., Iadicicco, C., Marchini, G., Kaur, M., Volpi, G., Patacchini, R., Singh, D., and Facchinetti, F. (2012). Cigarette smoke and its component acrolein augment IL-8/CXCL8 mRNA stability via p38 MAPK/MK2 signaling in human pulmonary cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 303, L929-L938.
86. Moretto, N., Facchinetti, F., Southworth, T., Civelli, M., Singh, D., and Patacchini, R. (2009). Alpha, beta-unsaturated aldehydes contained in cigarette smoke elicit IL-8 release in pulmonary cells through mitogen-activated protein kinases. Am. J. Physiol. Lung Cell. Mol. Physiol. 296, L839-L848.
87. Myers, C. R., Myers, J. M., Kufahl, T. D., Forbes, R., and Szadkowski, A. (2011). The effects of acrolein on the thioredoxin system: implications for redox-sensitive signaling. Mol. Nutr. Food Res. 55, 1361-1374.
88. Nakamura, M., Tomitori, H., Suzuki, T., Sakamoto, A., Terui, Y., Saiki, R., Dohmae, N., Igarashi, K., and Kashiwagi, K. (2013). Inactivation of GAPDH as one mechanism of acrolein toxicity. Biochem. Biophys. Res. Commun. 430, 1265-1271.
89. O'Toole, T. E., Abplanalp, W., Li, X., Cooper, N., Conklin, D. J., Haberzettl, P., and Bhatnagar, A. (2014). Acrolein decreases endothelial cell migration and insulin sensitivity through induction of Let-7a. Toxicol. Sci. 140, 271-282.
90. O'Toole, T. E., Zheng, Y. T., Hellmann, J., Conklin, D. J., Barski, O., and Bhatnagar, A. (2009). Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages. Toxicol. Appl. Pharmacol. 236, 194-201.
91. Ong, F. H., Henry, P. J., and Burcham, P. C. (2012). Prior exposure to acrolein accelerates pulmonary inflammation in influenza A-infected mice. Toxicol. Lett. 212, 241-251.
92. Park, J., Zheng, L., Marquis, A., Walls, M., Duerstock, B., Pond, A., Vega-Alvarez, S., Wang, H., Ouyang, Z., and Shi, R. (2014). Neuroprotective role of hydralazine in rat spinal cord injuryattenuation of acrolein-mediated damage. J. Neurochem. 129, 339-349.
93. Pawlowicz, A. J. and Kronberg, L. (2008). Characterization of adducts formed in reactions of acrolein with thymidine and calf thymus DNA. Chem. Biodivers. 5, 177-188.
94. Pawlowicz, A. J., Munter, T., Klika, K. D., and Kronberg, L. (2006a). Reaction of acrolein with 2'-deoxyadenosine and 9-ethyladenine-formation of cyclic adducts. Bioorg. Chem. 34, 39-48.
95. Pawlowicz, A. J., Munter, T., Zhao, Y., and Kronberg, L. (2006b). Formation of acrolein adducts with 2'-deoxyadenosine in calf thymus DNA. Chem. Res. Toxicol. 19, 571-576.
96. Perez, C. M., Ledbetter, A. D., Hazari, M. S., Haykal-Coates, N., Carll, A. P., Winsett, D. W., Costa, D. L., and Farraj, A. K. (2013). Hypoxia stress test reveals exaggerated cardiovascular effects in hypertensive rats after exposure to the air pollutant acrolein. Toxicol. Sci. 132, 467-477.
97. Pizzimenti, S., Ciamporcero, E., Daga, M., Pettazzoni, P., Arcaro, A., Cetrangolo, G., Minelli, R., Dianzani, C., Lepore, A., Gentile, F., and Barrera, G. (2013). Interaction of aldehydes derived from lipid peroxidation and membrane proteins. Front. Physiol. 4, 242.
98. Pugazhenthi, S., Phansalkar, K., Audesirk, G., West, A., and Cabell, L. (2006). Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal. Free Radic. Biol. Med. 40, 21-34.
99. Ranganna, K., Yousefipour, Z., Nasif, R., Yatsu, F. M., Milton, S. G., and Hayes, B. E. (2002). Acrolein activates mitogen-activated protein kinase signal transduction pathways in rat vascular smooth muscle cells. Mol. Cell. Biochem. 24, 83-98.
100. Ribeiro, C. M. and O'Neal, W. K. (2012). Endoplasmic reticulum stress in chronic obstructive lung diseases. Curr. Mol. Med. 12, 872-882.
101. Rom, O., Kaisari, S., Aizenbud, D., and Reznick, A. Z. (2013). The effects of acetaldehyde and acrolein on muscle catabolism in C2 myotubes. Free Radic. Biol. Med. 65C, 190-200.
102. Roy, J., Pallepati, P., Bettaieb, A., and Averill-Bates, D. A. (2010). Acrolein induces apoptosis through the death receptor pathway in A549 lung cells: role of p53. Can. J. Physiol. Pharmacol. 88, 353-368.
103. Roy, J., Pallepati, P., Bettaieb, A., Tanel, A., and Averill-Bates, D. A. (2009). Acrolein induces a cellular stress response and triggers mitochondrial apoptosis in A549 cells. Chem. Biol. Int. 181, 154-167.
104. Sarkar, P. and Hayes, B. E. (2007). Induction of COX-2 by acrolein in rat lung epithelial cells. Mol. Cell. Biochem. 301, 191-199.
105. Seiner, D. R., LaButti, J. N., and Gates, K. S. (2007). Kinetics and mechanism of protein tyrosine phosphatase 1B inactivation by acrolein. Chem. Res. Toxicol. 20, 1315-1320.
106. Shao, B. (2012). Site-specific oxidation of apolipoprotein A-I impairs cholesterol export by ABCA1, a key cardioprotective function of HDL. Biochim. Biophys. Acta 1821, 490-501.
107. Shi, Y., Sun, W., McBride, J. J., Cheng, J. X., and Shi, R. (2011). Acrolein induces myelin damage in mammalian spinal cord. J. Neurochem. 117, 554-564.
108. Song, J. J., Lee, J. D., Lee, B. D., Chae, S. W., and Park, M. K. (2013). Effect of acrolein, a hazardous air pollutant in smoke, on human middle ear epithelial cells. Int. J. Pediatr. Otorhinolaryngol. 77, 1659-1664.
109. Srivastava, S., Sithu, S. D., Vladykovskaya, E., Haberzettl, P., Hoetker, D. J., Siddiqui, M. A., Conklin, D. J., D'Souza, S. E., and Bhatnagar, A. (2011). Oral exposure to acrolein exacerbates atherosclerosis in apoE-null mice. Atherosclerosis 215, 301-308.
110. Stevens, J. F. and Maier, C. S. (2008). Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. Mol. Nutr. Food Res. 52, 7-25.
111. Sun, L., Luo, C., Long, J., Wei, D., and Liu, J. (2006). Acrolein is a mitochondrial toxin: effects on respiratory function and enzyme activities in isolated rat liver mitochondria. Mitochondrion 6, 136-142.
112. Sun, Y., Ito, S., Nishio, N., Tanaka, Y., Chen, N., and Isobe, K. I. (2014). Acrolein induced both pulmonary inflammation and the death of lung epithelial cells. Toxicol. Lett. 229, 384-392.
113. Tanel, A. and Averill-Bates, D. A. (2005). The aldehyde acrolein induces apoptosis via activation of the mitochondrial pathway. Biochim. Biophys. Acta 1743, 255-267.
114. Tanel, A. and Averill-Bates, D. A. (2007a). Activation of the death receptor pathway of apoptosis by the aldehyde acrolein. Free Radic. Bio. Med. 42, 798-810.
115. Tanel, A. and Averill-Bates, D. A. (2007b). Inhibition of acroleininduced apoptosis by the antioxidant N-acetylcysteine. J. Pharmacol. Exp. Ther. 321, 73-83.
116. Tanel, A., Pallepati, P., Bettaieb, A., Morin, P., and Averill-Bates, D. A. (2014). Acrolein activates cell survival and apoptotic death responses involving the endoplasmic reticulum in A549 lung cells. Biochim. Biophys. Acta 1843, 827-835.
117. Tang, M. S., Wang, H. T., Hu, Y., Chen, W. S., Akao, M., Feng, Z., and Hu, W. (2011). Acrolein induced DNA damage, mutagenicity and effect on DNA repair. Mol. Nutr. Food Res. 55, 1291-1300.
118. Toxicological Profile For ACROLEIN. (2007). Available at: http://www.atsdr.cdc.gov/ToxProfiles/tp124.pdf. Accessed November 10, 2014.
119. Tran, T. N., Kosaraju, M. G., Tamamizu-Kato, S., Akintunde, O., Zheng, Y., Bielicki, J. K., Pinkerton, K., Uchida, K., Lee, Y. Y., and Narayanaswami, V. (2014). Acrolein modification impairs key functional features of rat apolipoprotein E: identification of modified sites by mass spectrometry. Biochemistry 53, 361-375.
120. Uchida, K., Kanematsu, M., Morimitsu, Y., Osawa, T., Noguchi, N., and Niki, E. (1998a). Acrolein is a product of lipid peroxidation reaction. Formation of free acrolein and its conjugate with lysine residues in oxidized low density lipoproteins. J. Biol. Chem. 273, 16058-16066.
121. Uchida, K., Kanematsu, M., Sakai, K., Matsuda, T., Hattori, N., Mizuno, Y., Suzuki, D., Miyata, T., Noguchi, N., Niki, E., and Osawa, T. (1998b). Protein-bound acrolein: potential markers for oxidative stress. Proc. Natl. Acad. Sci. U.S.A. 95, 4882-4887.
122. Vacaru, A. M., Di Narzo, A. F., Howarth, D. L., Tsedensodnom, O., Imrie, D., Cinaroglu, A., Amin, S., Hao, K., and Sadler, K. C. (2014). Molecularly defined unfolded protein response subclasses have distinct correlations with fatty liver disease in zebrafish. Dis. Model. Mech. 7, 823-835.
123. Valacchi, G., Pagnin, E., Phung, A., Nardini,M., Schock, B. C., Cross, C. E., and van der Vliet, A. (2005). Inhibition of NFkappaB activation and IL-8 expression in human bronchial epithelial cells by acrolein. Antioxid. Redox Signal. 7, 25-31.
124. van der Toorn, M., Smit-de Vries, M. P., Slebos, D. J., de Bruin, H. G., Abello, N., van Oosterhout, A. J., Bischoff, R., and Kauffman, H. F. (2007). Cigarette smoke irreversibly modifies glutathione in airway epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 293, L1156-L1162.
125. Vidro-Kotchan, E., Yendluri, B. B., Le-Thai, T., and Tsin, A. (2011). NBHA reduces acrolein-induced changes in ARPE-19 cells: possible involvement of TGFbeta. Curr. Eye Res. 36, 370-378.
126. Volpi, G., Facchinetti, F., Moretto, N., Civelli, M., and Patacchini, R. (2011). Cigarette smoke and alpha, beta-unsaturated aldehydes elicit VEGF release through the p38 MAPK pathway in human airway smooth muscle cells and lung fibroblasts. Br. J. Pharmacol. 163, 649-661.
127. Von Tungeln, L. S., Yi, P., Bucci, T. J., Samokyszyn, V. M., Chou, M. W., Kadlubar, F. F., and Fu, P. P. (2002). Tumorigenicity of chloral hydrate, trichloroacetic acid, trichloroethanol, malondialdehyde, 4-hydroxy-2-nonenal, crotonaldehyde, and acrolein in the B6C3F(1) neonatal mouse. Cancer Lett. 185, 13-19.
128. Voulgaridou, G. P., Anestopoulos, I., Franco, R., Panayiotidis, M. I., and Pappa, A. (2011). DNA damage induced by endogenous aldehydes: current state of knowledge. Mutat. Res. 711, 13-27.
129. Wang, G. W., Guo, Y., Vondriska, T. M., Zhang, J., Zhang, S., Tsai, L. L., Zong, N. C., Bolli, R., Bhatnagar, A., and Prabhu, S. D. (2008). Acrolein consumption exacerbates myocardial ischemic injury and blocks nitric oxide-induced PKCepsilon signaling and cardioprotection. J. Mol. Cell. Cardiol. 44, 1016-1022.
130. Wang, H. T., Hu, Y., Tong, D., Huang, J., Gu, L., Wu, X. R., Chung, F. L., Li, G. M., and Tang, M. S. (2012). Effect of carcinogenic acrolein on DNA repair and mutagenic susceptibility. J. Biol. Chem. 287, 12379-12386.
131. Wang, T., Liu, Y., Chen, L., Wang, X., Hu, X. R., Feng, Y. L., Liu, D. S., Xu, D., Duan, Y. P., Lin, J., et al. (2009). Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats. Eur. Respir. J. 33, 1122-1132.
132. Wang, L., Sun, Y., Asahi, M., and Otsu, K. (2011). Acrolein, an environmental toxin, induces cardiomyocyte apoptosis via elevated intracellular calcium and free radicals. Cell Biochem. Biophys. 61, 131-136.
133. Wang, H. T., Weng, M. W., Chen, W. C., Yobin, M., Pan, J., Chung, F. L., Wu, X. R., Rom, W., and Tang, M. S. (2013). Effect of CpG methylation at different sequence context on acrolein- and BPDE-DNA binding and mutagenesis. Carcinogenesis 34, 220-227.
134. Watanabe, K., Nakazato, Y., Saiki, R., Igarashi, K., Kitada, M., and Ishii, I. (2013). Acrolein-conjugated low-density lipoprotein induces macrophage foam cell formation. Atherosclerosis 227, 51-57.
135. Watzek, N., Scherbl, D., Feld, J., Berger, F., Doroshyenko, O., Fuhr, U., Tomalik-Scharte, D., Baum, M., Eisenbrand, G., and Richling, E. (2012). Profiling of mercapturic acids of acrolein and acrylamide in human urine after consumption of potato crisps. Mol. Nutr. Food Res. 56, 1825-1837.
136. Wu, C. C., Hsieh, C. W., Lai, P. H., Lin, J. B., Liu, Y. C., and Wung, B. S. (2006). Upregulation of endothelial heme oxygenase-1 expression through the activation of the JNK pathway by sublethal concentrations of acrolein. Toxicol. Appl. Pharmacol. 214, 244-252.
137. Yadav, U. C. and Ramana, K. V. (2013). Regulation of NF-kappaBinduced inflammatory signaling by lipid peroxidationderived aldehydes. Oxid. Med. Cell. Longev. 2013, 690545.
138. Yoshida, M., Mikami, T., Higashi, K., Saiki, R., Mizoi, M., Fukuda, K., Nakamura, T., Ishii, I., Nishimura, K., Toida, T., et al. (2012). Inverse correlation between stroke and urinary 3-hydroxypropyl mercapturic acid, an acrolein-glutathione metabolite. Clin. Chim. Acta 413, 753-759.
139. Zarkovic, N., Cipak, A., Jaganjac, M., Borovic, S., and Zarkovic, K. (2013). Pathophysiological relevance of aldehydic protein modifications. J. Proteomics 92, 239-247.
140. Zhang, H. and Forman, H. J. (2008). Acrolein induces heme oxygenase-1 through PKC-delta and PI3K in human bronchial epithelial cells. Am. J. Respir. Cell Mol. Biol. 38, 483-490.
141. Zheng, L., Park, J., Walls, M., Tully, M., Jannasch, A., Cooper, B., and Shi, R. (2013). Determination of urine 3-HPMA, a stable acrolein metabolite in a rat model of spinal cord injury. J. Neurotrauma 30, 1334-1341.
142. Zhou, A. X. and Tabas, I. (2013). The UPR in atherosclerosis. Semin. Immunopathol. 35, 321-332.
143. Zhu, L., Liu, Z., Feng, Z.,Hao, J., Shen,W., Li,X., Sun, L., Sharman, E., Wang, Y.,Wertz, K., et al. (2010). Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells. J. Nutr. Biochem. 21, 1089-1098.