Inhibition of Hydrogen peroxide signaling by 4-hydroxynonenal due to differential regulation of Akt1 and Akt2 contributes to decreases in cell survival and proliferation in hepatocellular carcinoma cells
Open accessAbstract
Dysregulation of cell signaling by electrophiles such as 4-hydroxynonenal (4-HNE) is a key component in the pathogenesis of chronic inflammatory liver disease. Another consequence of inflammation is the perpetuation of oxidative damage by the production of reactive oxidative species such as hydrogen peroxide. Previously, we have demonstrated Akt2 as a direct target of 4-HNE in hepatocellular carcinoma cells. In the present study, we used the hepatocellular carcinoma cell line HepG2 as model to understand the combinatorial effects of 4-HNE and hydrogen peroxide. We demonstrate that 4-HNE inhibits hydrogen peroxide-mediated phosphorylation of Akt1 but not Akt2. Pretreatment of HepG2 cells with 4-HNE prevented hydrogen peroxide stimulation of Akt-dependent phosphorylation of downstream targets and intracellular Akt activity compared with untreated control cells. Using biotin hydrazide capture, it was confirmed that 4-HNE treatment resulted in carbonylation of Akt1, which was not observed in untreated control cells. Using a synthetic GSK3α/β peptide as a substrate, treatment of recombinant human myristoylated Akt1 (rAkt1) with 20 or 40 μΜ 4-HNE inhibited rAkt1 activity by 29 and 60%, respectively. We further demonstrate that 4-HNE activates Erk via a PI3 kinase and PP2A-dependent mechanism leading to increased Jnk phosphorylation. At higher concentrations, 4-HNE decreased both cell survival and proliferation as evidenced by MTT assays and EdU incorporation as well as decreased expression of cyclin D1 and β-catenin, an effect only moderately increased by the addition of hydrogen peroxide. The ability of 4-HNE to exert combinatorial effects on Erk, Jnk, and Akt-dependent cell survival pathways provides additional insight into the mechanisms of cellular damage associated with chronic inflammation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
After ethanol intake, AA, MDA, and 4-HNE adducts are produced rapidly in the hepatic centrilobular zone, sinusoids, and HSCs as well as on the hepatocyte surface; their amounts are markedly elevated in the early phase of ALD, suggesting a role in initial development and progression of ALD.
“After ethanol intake, AA, MDA, and 4-HNE adducts are produced rapidly in the hepatic centrilobular zone (zone III), sinusoids, and HSCs as well as on the hepatocyte surface in the liver.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [219]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mosmann, T. (1983) · Journal of Immunological Methods · doi:10.1016/0022-1759(83)90303-4 · Cited by 56,104 · see citing works
Reversible Inactivation of the Tumor Suppressor PTEN by H2O2
Lee, S.-R., Yang, K., Kwon, J., Lee, C., Jeong, W., & Rhee, S. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111899200 · Cited by 1,061 · see citing works
Nogueira, V., Park, Y., Chen, C.-C., Xu, P.-Z., Chen, M.-L., Tonic, I., Unterman, T., & Hay, N. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.11.003 · Cited by 780 · see citing works
β-Catenin destruction complex: insights and questions from a structural perspective
Kimelman, D., & Xu, W. (2006) · Oncogene · doi:10.1038/sj.onc.1210055 · Cited by 628 · cited 1× · see citing works
“In a recent report, decreased GSK3b phosphorylation promoted GSK3b activation and degradation of b-catenin [55].”
JNK1 but not JNK2 promotes the development of steatohepatitis in mice
Schattenberg, J. M., Singh, R., Wang, Y., Lefkowitch, J. H., Rigoli, R. M., Scherer, P. E., & Czaja, M. J. (2006) · Hepatology · doi:10.1002/hep.20999 · Cited by 384 · see citing works
Physiological regulation of Akt activity and stability.
Liao, Y., & Hung, M. (2010) · PubMed Central · Cited by 343 · see citing works
Protein phosphatase 2A: the Trojan Horse of cellular signaling
Sontag, E. (2001) · Cellular Signalling · doi:10.1016/s0898-6568(00)00123-6 · Cited by 328 · see citing works
HNE interacts directly with JNK isoforms in human hepatic stellate cells.
Parola, M., Robino, G., Marra, F., Pinzani, M., Bellomo, G., Leonarduzzi, G., Chiarugi, P., Camandola, S., Poli, G., Waeg, G., et al. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1413 · Cited by 297 · see citing works
C–Jun–N–Terminal Kinase Drives Cyclin D1 Expression and Proliferation During Liver Regeneration
Schwabe, R. F., Bradham, C. A., Uehara, T., Hatano, E., Bennett, B. L., Schoonhoven, R., & Brenner, D. A. (2003) · Hepatology · doi:10.1053/jhep.2003.50135 · Cited by 251 · see citing works
Maroulakou, I. G., Oemler, W., Naber, S. P., & Tsichlis, P. N. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3782 · Cited by 237 · see citing works
In situ detection of lipid peroxidation by-products in chronic liver diseases
Paradis, V., Kollinger, M., Fabre, M., Holstege, A., Poynard, T., & Bedossa, P. (1997) · Hepatology · doi:10.1053/jhep.1997.v26.pm0009214462 · Cited by 228 · see citing works
Paradis, V., Mathurin, P., Kollinger, M., Imbert‐Bismut, F., Charlotte, F., Piton, A., Opolon, P., Holstege, A., Poynard, T., & Bédossa, P. (1997) · Journal of Clinical Pathology · doi:10.1136/jcp.50.5.401 · Cited by 195 · see citing works
Vila, A., Tallman, K. A., Jacobs, A. T., Liebler, D. C., Porter, N. A., & Marnett, L. J. (2008) · Chemical Research in Toxicology · doi:10.1021/tx700347w · Cited by 192 · see citing works
Akt2 Regulates Cardiac Metabolism and Cardiomyocyte Survival
DeBosch, B. J., Sambandam, N., Weinheimer, C. J., COURTOIS, M. R., & Muslin, A. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513087200 · Cited by 163 · see citing works
Saxena, N. K., Fu, P. P., Nagalingam, A., Wang, J., Handy, J. A., Cohen, C., Tighiouart, M., Sharma, D., & Anania, F. A. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.07.001 · Cited by 155 · see citing works
Ghatak, S., Biswas, A., Dhali, G. K., Chowdhury, A., Boyer, J. L., & Santra, A. K. (2010) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2010.11.016 · Cited by 150 · see citing works
Global Analysis of Protein Damage by the Lipid Electrophile 4-Hydroxy-2-nonenal
Codreanu, S. G., Zhang, B., Sobecki, S. M., Billheimer, D. D., & Liebler, D. C. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m800070-mcp200 · Cited by 146 · see citing works
Shao, Z., Bhattacharya, K., Hsich, E., Park, L., Walters, B. M., Germann, U. A., Wang, Y., Kyriakis, J. M., Mohanlal, R. W., Kuida, K., et al. (2005) · Circulation Research · doi:10.1161/01.res.0000197781.20524.b9 · Cited by 125 · see citing works
Augè, N., Garcia, V., Maupas‐Schwalm, F., Levade, T., Salvayre, R., & Nègre‐Salvayre, A. (2002) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000043453.21629.3b · Cited by 125 · see citing works
Moro, L., Arbini, A., Yao, J., di Sant'Agnese, P. A., Marra, E., & Gréco, M. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.178 · Cited by 124 · see citing works
Regulation of cyclin D1 gene expression
Witzel, I., Koh, L. F., & Perkins, N. D. (2010) · Biochemical Society Transactions · doi:10.1042/bst0380217 · Cited by 119 · see citing works
Mechanisms of 4-Hydroxy-2-nonenal Induced Pro- and Anti-Apoptotic Signaling
Chaudhary, P., Sharma, R., Sharma, A., Vatsyayan, R., Yadav, S., Singhal, S. S., Rauniyar, N., Prókai, L., Awasthi, S., & Awasthi, S. (2010) · Biochemistry · doi:10.1021/bi100517x · Cited by 114 · see citing works
4-Hydroxynonenal induces p53-mediated apoptosis in retinal pigment epithelial cells
Sharma, A., Sharma, R., Chaudhary, P., Vatsyayan, R., Pearce, V. P., Jeyabal, P., Zimniak, P., Awasthi, S., & Awasthi, S. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.09.016 · Cited by 104 · see citing works
Li (2009) · International Journal of Oncology · doi:10.3892/ijo_00000306 · Cited by 101 · see citing works
Oxidant-mediated Akt Activation in Human RPE Cells
Yang, P., Peairs, J. J., Tano, R., & Jaffe, G. J. (2006) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0140 · Cited by 98 · see citing works
Zhou, T., Zhou, K., Lee, K., Gao, G., Lyons, T. J., Kowluru, A., & Ma, J.-X. (2010) · Diabetologia · doi:10.1007/s00125-010-1943-1 · Cited by 93 · see citing works
Parekh, P. R., Motiwale, L., Naik, N. R., & Rao, K. V. K. (2010) · Experimental and Toxicologic Pathology · doi:10.1016/j.etp.2009.11.005 · Cited by 87 · see citing works
Phosphatase-Mediated Crosstalk Control of ERK and p38 MAPK Signaling in Corneal Epithelial Cells
Wang, Z., Yang, H., Tachado, S. D., Capo´-Aponte, J. E., Bildin, V. N., Koziel, H., & Reinach, P. S. (2006) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.06-0642 · Cited by 82 · see citing works
FTY720 induces apoptosis of human hepatoma cell lines through PI3-K-mediated Akt dephosphorylation
Lee, T. K., Man, K., Ho, J. W., Sun, C. K.-W., Ng, K. T., Wang, X. H., Wong, Y. C., Ng, I. O., Xu, R., & Fan, S. T. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh250 · Cited by 79 · see citing works
Ponce, D. P., Maturana, J. L., Cabello, P., Yefi, R., Niechi, I., Silva-Pavez, E., Armisén, R., Galindo, M. A., Antonelli, M., & Tapia, J. C. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22527 · Cited by 78 · see citing works
Stewart, B. J., Doorn, J. A., & Petersen, D. R. (2007) · Chemical Research in Toxicology · doi:10.1021/tx700106v · Cited by 77 · see citing works
Self-citationId-1 activates Akt-mediated Wnt signaling and p27Kip1 phosphorylation through PTEN inhibition
Lee, J.-Y., Kang, M.-B., Sh, J., Qian, T., Kim, H.-J., Kim, C., Kim, Y. D., & Kong, G. (2008) · Oncogene · doi:10.1038/onc.2008.451 · Cited by 74 · see citing works
Sharma, R., Sharma, A., Dwivedi, S., Zimniak, P., Awasthi, S., & Awasthi, S. (2007) · Biochemistry · doi:10.1021/bi701559f · Cited by 74 · see citing works
Santi, S. A., & Lee, H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014614 · Cited by 74 · see citing works
Modification of Akt2 by 4-Hydroxynonenal Inhibits Insulin-Dependent Akt Signaling in HepG2 Cells
Shearn, C. T., Fritz, K. S., Reigan, P., & Petersen, D. R. (2011) · Biochemistry · doi:10.1021/bi200029w · Cited by 73 · see citing works
Self-citationCovey, T. M., Edes, K., Coombs, G. S., Virshup, D. M., & Fitzpatrick, F. A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013545 · Cited by 72 · see citing works
Oxidized LDL and 4-hydroxynonenal modulate tyrosine kinase receptor activity
Nègre‐Salvayre, A., Vieira, O. V., Escargueil‐Blanc, I., & Salvayre, R. (2003) · Molecular Aspects of Medicine · doi:10.1016/s0098-2997(03)00020-7 · Cited by 70 · see citing works
Gas6 deficiency prevents liver inflammation, steatohepatitis, and fibrosis in mice
Fourcot, A., Couchie, D., Chobert, M.-N., Zafrani, E., Mavier, P., Laperche, Y., & Brouillet, A. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00311.2010 · Cited by 69 · see citing works
Reactive Lipid Species from Cyclooxygenase-2 Inactivate Tumor Suppressor LKB1/STK11
Wagner, T. M., Mullally, J. E., & Fitzpatrick, F. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509723200 · Cited by 62 · see citing works
Deletion of Akt1 causes heart defects and abnormal cardiomyocyte proliferation
Chang, Z., Zhang, Q., Feng, Q., Xu, J., Teng, T., Luan, Q., Shan, C., Hu, Y., Hemmings, B. A., Gao, X., et al. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.08.033 · Cited by 57 · see citing works
Pettazzoni, P., Pizzimenti, S., Toaldo, C., Sotomayor, P. C., Tagliavacca, L., Liu, S., Wang, D., Minelli, R., Ellis, L., Atadja, P. W., et al. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.11.011 · Cited by 53 · see citing works
Shearn, C. T., McCullough, R. L., Stewart, B. J., Fritz, K. S., Galligan, J. J., Hail, N., & Petersen, D. R. (2011) · Molecular Pharmacology · doi:10.1124/mol.110.069534 · Cited by 51 · see citing works
Self-citationDecreased expression of peroxiredoxin 6 in a mouse model of ethanol consumption
Roede, J. R., Stewart, B. J., & Petersen, D. R. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.08.032 · Cited by 43 · see citing works
Self-citationCheung, S., Kornelson, J. C., Al-Alwan, M. M., & Marshall, A. J. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2006.10.013 · Cited by 38 · see citing works
Lin, C., Ho, H., Cheng, M., Cheng, T.-H., Yu, J., & Chiu, D. T.-Y. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.04.019 · Cited by 36 · see citing works
Akiba, S., Kumazawa, S., Yamaguchi, H., Hontani, N., Matsumoto, T., Ikeda, T., Oka, M., & Sato, T. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.06.003 · Cited by 33 · see citing works
Roede, J. R., Orlicky, D. J., Fisher, A. B., & Petersen, D. R. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.152983 · Cited by 33 · see citing works
Self-citationNemoto, T., Kanai, T., Yanagita, T., Satoh, S., Maruta, T., Yoshikawa, N., Kobayashi, H., & Wada, A. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.02.075 · Cited by 31 · see citing works
Thiol redox systems and protein kinases in hepatic stellate cell regulatory processes
Brunati, A. M., Pagano, M. A., Bindoli, A., & Rigobello, M. P. (2010) · Free Radical Research · doi:10.3109/10715760903555836 · Cited by 31 · see citing works
Zhang, L., Sun, S., Zhou, J., Liu, J., Lv, J.-H., Yu, X.-Q., Li, C., Gong, L., Yan, Q., Deng, M., et al. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3560 · Cited by 30 · see citing works
Pikkarainen, S., Kennedy, R., Marshall, A. K., Tham, E. L., Lay, K., Kriz, T. A., Handa, B. S., Clerk, A., & Sugden, P. H. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.037887 · Cited by 26 · see citing works
WANG, X., Meng, X., SUN, X., LIU, B., HAN, M., Du, Y., SONG, Y., & Xu, W. (2011) · Neoplasma · doi:10.4149/neo_2011_03_239 · Cited by 24 · see citing works
Lipid aldehyde-mediated cross-linking of apolipoprotein B-100 inhibits secretion from HepG2 cells
Stewart, B. J. R., Roede, J. R., Doorn, J. A., & Petersen, D. R. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.04.004 · Cited by 23 · see citing works
Self-citationLim, J.-H., Lee, Y., Chun, Y., & Park, J. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00892.x · Cited by 15 · see citing works
Mammalian target of rapamycin regulates expression of β-catenin in hepatocellular carcinoma.
Feng, Z.-B., Fan, X., Jiao, Y., & Ban, K. (2011) · Human Pathology · doi:10.1016/j.humpath.2010.07.021 · Cited by 12 · see citing works
Flagged first, then by citations
2 of the 57 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Ayala, A., Muñoz, M., & Argüelles, S. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/360438 · Cited by 6,561 · see citing works
A simple ImageJ macro tool for analyzing mitochondrial network morphology in mammalian cell culture
Valente, A. J. F., Maddalena, L. A., Robb, E. L., Moradi, F., & Stuart, J. A. (2017) · Acta Histochemica · doi:10.1016/j.acthis.2017.03.001 · Cited by 860 · see citing works
Protein carbonylation as a major hallmark of oxidative damage: Update of analytical strategies
Fedorova, M., Bollineni, R. C., & Hoffmann, R. (2013) · Mass Spectrometry Reviews · doi:10.1002/mas.21381 · Cited by 516 · see citing works
Rungratanawanich, W., Qu, Y., Wang, X., Essa, M. M., & Song, B.-J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00561-7 · Cited by 411 · see citing works
Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review)
Nițulescu, G. M., Margina, D. M., Juzenas, P., Peng, Q., Olaru, O. T., Saloustros, E. S., Fenga, C., Spandidos, D. A., Libra, M., & Tsatsakis, A. M. (2015) · International Journal of Oncology · doi:10.3892/ijo.2015.3306 · Cited by 370 · see citing works
The role of oxidative stress on breast cancer development and therapy
Hecht, F., Pessôa, C. F., Gentile, L. B., Rosenthal, D., de Carvalho, D. P., & Fortunato, R. S. (2016) · Tumor Biology · doi:10.1007/s13277-016-4873-9 · Cited by 304 · see citing works
Reactive Oxygen Species Bridge the Gap between Chronic Inflammation and Tumor Development
Yu, W., Tu, Y., Long, Z., Liu, J., Kong, D., Peng, J., Wu, H., Zheng, G., Zhao, J., Chen, Y., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/2606928 · Cited by 161 · see citing works
Lipid oxidation products in the pathogenesis of non-alcoholic steatohepatitis
Bellanti, F., Villani, R., Facciorusso, A., Vendemiale, G., & Serviddio, G. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.01.023 · Cited by 132 · see citing works
4-hydroxynonenal-mediated signaling and aging
Zhang, H., & Forman, H. J. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.11.032 · Cited by 114 · see citing works
Milković, L., Gašparović, A. Č., & Žarković, N. (2014) · Free Radical Research · doi:10.3109/10715762.2014.999056 · Cited by 84 · see citing works
Cancer growth regulation by 4-hydroxynonenal
Gašparović, A. Č., Milković, L., Šunjić, S. B., & Žarković, N. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.01.030 · Cited by 72 · see citing works
Proatherogenic effects of 4-hydroxynonenal
Nègre‐Salvayre, A., Garoby-Salom, S., Swiader, A., Rouahi, M., Pucelle, M., & Salvayre, R. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.038 · Cited by 69 · see citing works
Besse‐Patin, A., & Estall, J. L. (2014) · International Journal of Cell Biology · doi:10.1155/2014/519153 · Cited by 58 · see citing works
Shearn, C. T., Backos, D. S., Orlicky, D. J., Smathers-McCullough, R. L., & Petersen, D. R. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.543942 · Cited by 57 · see citing works
Self-citationJi, Y. S., Dai, Z., Wu, G., & Wu, Z. (2016) · Scientific Reports · doi:10.1038/srep32929 · Cited by 55 · see citing works
Foo, J. B., Yazan, L. S., Tor, Y. S., Nurdin, A., Ismail, N., Imam, M. U., Yeap, S. K., Cheah, Y. K., Abdullah, R., & Ismail, M. (2014) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-14-197 · Cited by 47 · see citing works
Sakai, O., Uchida, T., Imai, H., & Ueta, T. (2016) · FEBS Open Bio · doi:10.1002/2211-5463.12141 · Cited by 46 · see citing works
Lipid Peroxidation Linking Diabetes and Cancer: The Importance of 4-Hydroxynonenal
Jaganjac, M., & Žarković, N. (2022) · Antioxidants and Redox Signaling · doi:10.1089/ars.2022.0146 · Cited by 39 · see citing works
Palma, L. M., Miquel, E., Lagos-Rodríguez, V., Barbeito, L., Cassina, A., & Cassina, P. (2018) · Neurotherapeutics · doi:10.1007/s13311-018-0659-7 · Cited by 38 · see citing works
Chen, P., Ko, I.-L., Lee, C.-L., Hu, H.-C., Chang, F., Wu, Y., Leu, Y., Wu, C., Lin, C.-Y., Pan, C.-Y., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.01.043 · Cited by 39 · see citing works
Kim, S., Kim, S. Y., Ku, H. J., Jeon, Y. H., Lee, H., Lee, J., Kwon, T. K., Park, K. M., & Park, J. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.11.008 · Cited by 37 · see citing works
Sakai, O., Yasuzawa, T., Yoshie, S., Ueta, T., Imai, H., Sawabe, A., & Ueshima, S. (2016) · Pathophysiology · doi:10.1016/j.pathophys.2016.11.002 · Cited by 35 · see citing works
Lei, C., Zhou, J., Kuang, D., Tang, J., Li, Y.-J., & Chen, X. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064148 · Cited by 31 · see citing works
Seike, T., Boontem, P., Yanagi, M., Li, S., Kido, H., Yamamiya, D., Nakagawa, H., Okada, H., Yamashita, T., Harada, K., et al. (2022) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2022.06.008 · Cited by 23 · see citing works
Ding, L., Wo, L., Du, Z., Tang, L., Song, Z., & Dou, X. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186357 · Cited by 24 · see citing works
Role of Glutathione Peroxidase 4 in Conjunctival Epithelial Cells
Sakai, O., Uchida, T., Imai, H., Ueta, T., & Amano, S. (2015) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-15463 · Cited by 21 · see citing works
Wang, F., Li, H., Li, Y., & Kong, L. (2020) · Biomolecules · doi:10.3390/biom10010146 · Cited by 18 · see citing works
Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis
Nègre‐Salvayre, A., & Salvayre, R. (2024) · Antioxidants · doi:10.3390/antiox13020232 · Cited by 18 · see citing works
Chen, X., Lv, Q., Ma, J., & Liu, Y. (2018) · Cell Proliferation · doi:10.1111/cpr.12437 · Cited by 16 · see citing works
Lagos-Rodríguez, V., Palma, L. M., Marton, S., Miquel, E., Escobar-Pintos, R., Cassina, A., Lago, N., & Cassina, P. (2020) · Pain · doi:10.1097/j.pain.0000000000001992 · Cited by 16 · see citing works
Tan, B. L., Norhaizan, M. E., & Chan, L. C. (2018) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2018/7826576 · Cited by 14 · see citing works
Role of Glutathione Peroxidase 4 in Corneal Endothelial Cells
Uchida, T., Sakai, O., Imai, H., & Ueta, T. (2016) · Current Eye Research · doi:10.1080/02713683.2016.1196707 · Cited by 13 · see citing works
Fu, A., Li, J., Ding, Q., Guo, R., Pi, A., Yang, W., Chen, Y., Dou, X., Song, Z., & Li, S. (2022) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.2c00852 · Cited by 13 · see citing works
Procaterol but Not Dexamethasone Protects 16HBE Cells From H2O2-Induced Oxidative Stress
Deng, Z. H., Zhou, J., Sun, S., Zhao, X., Sun, Y., & Pu, X. (2014) · Journal of Pharmacological Sciences · doi:10.1254/jphs.13206fp · Cited by 10 · see citing works
Kasamatsu, A., Nozaki, R., Kawasaki, K., Saito, T., Minemura, C., Seki, N., Moss, J., & Uzawa, K. (2024) · Cancers · doi:10.3390/cancers16061242 · Cited by 5 · see citing works
Lizeth, A.-N. M., Blas-Valdivia, V., del Rocio, T.-B. M., Franco-Colín, M., Damián, J.-M., Cruz-Orea, A., Cano-Europa, E., & Rojas-Franco, P. (2024) · Applied Spectroscopy · doi:10.1177/00037028231222508 · Cited by 3 · see citing works
Mass Spectrometry‐Based Platforms for Protein Lipoxidation Profiling
Tang, Z., Wang, T., & Liu, C. (2024) · Chemistry - A European Journal · doi:10.1002/chem.202402062 · Cited by 2 · see citing works
Xiao, H., Wang, B., Xiong, S., Li, C., Ding, Y., Chao, D., Mei, B., Shen, N., & Luo, G. (2025) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s495151 · Cited by 3 · see citing works
Alox8 knockout exacerbates imiquimod-induced psoriasis-like inflammation
Palmer, M. A., Kirchhoff, R., Hahnefeld, L., Thomas, D., Elewa, M. A. F., You, X., Aliraj, B., Benatzy, Y., Weigert, A., Schebb, N. H., et al. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08727-9 · Cited by 1 · see citing works
Li, X., He, X., Huang, Z., Liu, X., Zhang, J., Gao, Y., Li, Q., & Yu, X. (2026) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.70483 · Cited by 1 · see citing works
Targeting redox regulatory site of protein kinase B impedes neutrophilic inflammation in lung injuryPreprint
Chen, P.-J., Ko, I.-L., Lee, C.-L., Hu, H.-C., Chang, F.-R., Wu, Y.-C., Leu, Y.-L., Wu, C.-C., Lin, C.-Y., Pan, C.-Y., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/264184
Peeking into a Hidden Syndicate: Mitochondria of the Human Amniotic Membrane
Weidinger, A., & Banerjee, A. (2019) · Springer eBooks · doi:10.1007/978-3-319-37076-7_64-1
- Authors
- Shearn, C. T., Reigan, P., & Petersen, D. R.
- Affiliations
- University of Colorado Denver (US)
- Corresponding author
- Petersen, Dennis R.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 53
- Issue
- 1
- Pages
- 1-11
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC3377776
- OpenAlex
- W2012388221
- Cited by
- 42
- References
- 57
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 2 · 2014: 6 · 2013: 3
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Cancer Center, University of Colorado
- National Institute on Alcohol Abuse and Alcoholism (R01AA009300, F32AA018613, R37AA009300)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK074487)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- 4-hydroxynonenal, hydrogen peroxide signaling, AKT1, AKT2, protein carbonylation, hepatocellular carcinoma, HepG2 cells, ERK activation, JNK phosphorylation, PI3-kinase, protein phosphatase 2A, cyclin D1, β-catenin, cell survival, cell proliferation, chronic inflammation, oxidative stress, electrophiles
- MeSH terms
- Aldehydes, Cell Survival, Carcinoma, Hepatocellular, Humans, Hydrogen Peroxide, Liver Neoplasms, Phosphorylation, Tumor Cells, Cultured, Blotting, Western, Signal Transduction, Cysteine Proteinase Inhibitors, Oxidants, Phosphatidylinositol 3-Kinases, Cell Proliferation, Proto-Oncogene Proteins c-akt
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
