{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:22:04Z","timestamp":1790256124074,"version":"4.1.0"},"reference-count":65,"publisher":"Spandidos Publications","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int J Mol Med"],"DOI":"10.3892\/ijmm.2020.4453","type":"journal-article","created":{"date-parts":[[2020,1,8]],"date-time":"2020-01-08T02:42:10Z","timestamp":1578451330000},"source":"Crossref","is-referenced-by-count":18,"title":["Metformin attenuates the D\u2011galactose\u2011induced aging process via the UPR through the AMPK\/ERK1\/2 signaling pathways"],"prefix":"10.3892","author":[{"given":"Hua","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoai","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xubo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2011Jia","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2249","published-online":{"date-parts":[[2020,1,8]]},"reference":[{"key":"key20200713162412_b1-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.heares.2012.04.012","article-title":"A long-term high-fat diet increases oxidative stress, mitochondrial damage and apoptosis in the inner ear of D-galactose-induced aging rats","volume":"287","author":"Du","year":"2012","journal-title":"Hear Res"},{"key":"key20200713162412_b2-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/S0140-6736(05)67423-5","article-title":"Presbycusis","volume":"366","author":"Gates","year":"2005","journal-title":"Lancet"},{"key":"key20200713162412_b3-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"635","DOI":"10.3766\/jaaa.23.8.5","article-title":"Central presbycusis: A review and evaluation of the evidence","volume":"23","author":"Humes","year":"2012","journal-title":"J Am Acad Audiol"},{"key":"key20200713162412_b4-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"a004440","DOI":"10.1101\/cshperspect.a004440","article-title":"Aging as an event of proteostasis collapse","volume":"3","author":"Taylor","year":"2011","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"key20200713162412_b5-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.cmet.2014.05.006","article-title":"Mitochondrial proteostasis in the control of aging and longevity","volume":"20","author":"Jensen","year":"2014","journal-title":"Cell Metab"},{"key":"key20200713162412_b6-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"5150","DOI":"10.1172\/JCI97498","article-title":"Deletion of Tmtc4 activates the unfolded protein response and causes postnatal hearing loss","volume":"128","author":"Li","year":"2018","journal-title":"J Clin Invest"},{"key":"key20200713162412_b7-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/fchem.2015.00005","article-title":"Can UPR integrate fasting and stem cell regeneration?","volume":"3","author":"Chaube","year":"2015","journal-title":"FRONT CHEM"},{"key":"key20200713162412_b8-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3389\/fnagi.2014.00008","article-title":"Memory loss in Alzheimer's disease: Are the alterations in the UPR network involved in the cognitive impairment?","volume":"6","author":"Duran-Aniotz","year":"2014","journal-title":"Front Aging Neurosci"},{"key":"key20200713162412_b9-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.tibs.2011.03.001","article-title":"Modulating stress responses by the UPRosome: A matter of life and death","volume":"36","author":"Woehlbier","year":"2011","journal-title":"Trends Biochem Sci"},{"key":"key20200713162412_b10-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.bbrc.2014.04.130","article-title":"Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice","volume":"448","author":"Zhao","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"key20200713162412_b11-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.neuroscience.2014.07.046","article-title":"Neuroprotective effect of metformin in MPTP-induced Parkinson's disease in mice","volume":"277","author":"Patil","year":"2014","journal-title":"Neuroscience"},{"key":"key20200713162412_b12-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1111\/nep.13430","article-title":"Metformin inhibits TGF-beta 1-induced MCP-1 expression through BAMBI-mediated suppression of MEK\/ERK1\/2 signalling","volume":"24","author":"Liang","year":"2019","journal-title":"Nephrology (Carlton)"},{"key":"key20200713162412_b13-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.brainresbull.2018.04.008","article-title":"Neuroprotective effects of metformin on traumatic brain injury in rats associated with NF-\u03baB and MAPK signaling pathway","volume":"140","author":"Tao","year":"2018","journal-title":"Brain Res Bull"},{"key":"key20200713162412_b14-ijmm-45-03-0715","doi-asserted-by":"crossref","DOI":"10.17226\/25801","volume-title":"Guide for the Care and Use of Laboratory Animals","author":"National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals","year":"2011"},{"key":"key20200713162412_b15-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.lfs.2016.02.024","article-title":"Metformin-induced protection against oxidative stress is associated with AKT\/mTOR restoration in PC12 cells","volume":"148","author":"Khallaghi","year":"2016","journal-title":"Life Sci"},{"key":"key20200713162412_b16-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.redox.2017.10.002","article-title":"The dual role of poly(ADP-ribose) polymerase-1 in modulating parthanatos and autophagy under oxidative stress in rat cochlear marginal cells of the stria vascularis","volume":"14","author":"Jiang","year":"2018","journal-title":"Redox Biol"},{"key":"key20200713162412_b17-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/978-1-59745-361-5_3","article-title":"Methods to detect biomarkers of cellular senescence: The senescence-associated beta-galactosidase assay","volume":"371","author":"Itahana","year":"2007","journal-title":"Methods Mol Biol"},{"key":"key20200713162412_b18-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.bbrc.2014.08.063","article-title":"Reduced expression of Connexin26 and its DNA promoter hypermethylation in the inner ear of mimetic aging rats induced by d-galactose","volume":"452","author":"Wu","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"key20200713162412_b19-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.bbrc.2006.03.060","article-title":"The effect of the mtDNA4834 deletion on hearing","volume":"344","author":"Kong","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"key20200713162412_b20-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/em.20050","article-title":"Development of a quantitative PCR (TaqMan) assay for relative mitochondrial DNA copy number and the common mitochondrial DNA deletion in the rat","volume":"44","author":"Nicklas","year":"2004","journal-title":"Environ Mol Mutagen"},{"key":"key20200713162412_b21-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"key20200713162412_b22-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"2758","DOI":"10.1111\/febs.13324","article-title":"Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: Changes to Trx2 in the auditory cortex","volume":"282","author":"Sun","year":"2015","journal-title":"FEBS J"},{"key":"key20200713162412_b23-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1002\/2211-5463.12220","article-title":"Activation of Wnt\/\u03b2-catenin signaling by lithium chloride attenuates d-galactose-induced neurodegeneration in the auditory cortex of a rat model of aging","volume":"7","author":"Xia","year":"2017","journal-title":"FEBS Open Bio"},{"key":"key20200713162412_b24-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.ejphar.2007.04.039","article-title":"Neuroprotective effect of catalpol against MPP(+)-induced oxidative stress in mesencephalic neurons","volume":"568","author":"Tian","year":"2007","journal-title":"Eur J Pharmacol"},{"key":"key20200713162412_b25-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1016\/j.exger.2006.04.008","article-title":"The relation between D-galactose injection and mitochondrial DNA 4834 bp deletion mutation","volume":"41","author":"Kong","year":"2006","journal-title":"Exp Gerontol"},{"key":"key20200713162412_b26-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"e88019","DOI":"10.1371\/journal.pone.0088019","article-title":"Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model","volume":"9","author":"Zeng","year":"2014","journal-title":"PLoS One"},{"key":"key20200713162412_b27-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/fnagi.2012.00005","article-title":"Unfolded protein stress in the endoplasmic reticulum and mitochondria: A role in neuro-degeneration","volume":"4","author":"Bernales","year":"2012","journal-title":"Front Aging Neurosci"},{"key":"key20200713162412_b28-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.exger.2015.07.003","article-title":"Impaired unfolded protein response in the degeneration of cochlea cells in a mouse model of age-related hearing loss","volume":"70","author":"Wang","year":"2015","journal-title":"Exp Gerontol"},{"key":"key20200713162412_b29-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.freeradbiomed.2019.09.005","article-title":"Oxidative stress induces different tissue dependent effects on Mutyh-deficient mice","volume":"143","author":"Chen","year":"2019","journal-title":"Free Radic Biol Med"},{"key":"key20200713162412_b30-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.tibs.2011.03.006","article-title":"The Ras-ERK and PI3K-mTOR pathways: Cross-talk and compensation","volume":"36","author":"Mendoza","year":"2011","journal-title":"Trends Biochem Sci"},{"key":"key20200713162412_b31-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1023\/A:1022417102206","article-title":"Establishment of the mimetic aging effect in mice caused by D-galactose","volume":"4","author":"Ho","year":"2003","journal-title":"Biogerontology"},{"key":"key20200713162412_b32-ijmm-45-03-0715","first-page":"888893","article-title":"Establishment of model with inner ear mimetic aging and mtDNA 4834 bp deletion in rats","volume":"20","author":"Kong","year":"2006","journal-title":"Lin Chuang Er Bi Yan Hou Ke Za Zhi"},{"key":"key20200713162412_b33-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.heares.2012.09.006","article-title":"Age-related decline of the cytochrome c oxidase subunit expression in the auditory cortex of the mimetic aging rat model associated with the common deletion","volume":"294","author":"Zhong","year":"2012","journal-title":"Hear Res"},{"key":"key20200713162412_b34-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.cell.2005.02.001","article-title":"Mitochondria, oxidants, and aging","volume":"120","author":"Balaban","year":"2005","journal-title":"Cell"},{"key":"key20200713162412_b35-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/nature05292","article-title":"Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases","volume":"443","author":"Lin","year":"2006","journal-title":"Nature"},{"key":"key20200713162412_b36-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"6383","DOI":"10.1113\/JP274334","article-title":"Proteostasis and ageing: Insights from long-lived mutant mice","volume":"595","author":"Sands","year":"2017","journal-title":"J Physiol"},{"key":"key20200713162412_b37-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"R551","DOI":"10.1016\/j.cub.2006.06.054","article-title":"Mitochondria: More than just a powerhouse","volume":"16","author":"McBride","year":"2006","journal-title":"Curr Biol"},{"key":"key20200713162412_b38-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1002\/jcb.21936","article-title":"Estrogenic control of mitochondrial function and biogenesis","volume":"105","author":"Klinge","year":"2008","journal-title":"J Cell Biochem"},{"key":"key20200713162412_b39-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1111\/j.1749-6632.2009.05039.x","article-title":"Mitochondrial metabolism and cancer","volume":"1177","author":"Weinberg","year":"2009","journal-title":"Ann N Y Acad Sci"},{"key":"key20200713162412_b40-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/nature12188","article-title":"Mitonuclear protein imbalance as a conserved longevity mechanism","volume":"497","author":"Houtkooper","year":"2013","journal-title":"Nature"},{"key":"key20200713162412_b41-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"4055","DOI":"10.1242\/jcs.01275","article-title":"Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones","volume":"117","author":"Yoneda","year":"2004","journal-title":"J Cell Sci"},{"key":"key20200713162412_b42-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nrm.2017.110","article-title":"The mitochondrial UPR: Mechanisms, physiological functions and implications in ageing","volume":"19","author":"Shpilka","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"key20200713162412_b43-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"610","DOI":"10.2174\/1567205013666151221145445","article-title":"Evidence for mitochondrial UPR gene activation in familial and sporadic Alzheimer's disease","volume":"13","author":"Beck","year":"2016","journal-title":"Curr Alzheimer Res"},{"key":"key20200713162412_b44-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.cmet.2012.02.013","article-title":"Impaired insulin\/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal","volume":"15","author":"Zarse","year":"2012","journal-title":"Cell Metab"},{"key":"key20200713162412_b45-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.exger.2006.03.014","article-title":"Mitochondrial DNA deletions and the aging heart","volume":"41","author":"Mohamed","year":"2006","journal-title":"Exp Gerontol"},{"key":"key20200713162412_b46-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"3635","DOI":"10.1007\/s11033-010-0476-5","article-title":"Increased mitochondrial DNA damage and decreased base excision repair in the auditory cortex of D-galactose-induced aging rats","volume":"38","author":"Chen","year":"2011","journal-title":"Mol Biol Rep"},{"key":"key20200713162412_b47-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1002\/(SICI)1097-4644(19990615)73:4<545::AID-JCB12>3.0.CO;2-Q","article-title":"Mitochondrial DNA deletions are associated with ischemia and aging in Balb\/c mouse brain","volume":"73","author":"Zeng","year":"1999","journal-title":"J Cell Biochem"},{"key":"key20200713162412_b48-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.brainres.2010.04.082","article-title":"Age-related changes in the central auditory system: Comparison of D-galactose-induced aging rats and naturally aging rats","volume":"1344","author":"Chen","year":"2010","journal-title":"Brain Res"},{"key":"key20200713162412_b49-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"3649","DOI":"10.1242\/jcs.153643","article-title":"Redox controls UPR to control redox","volume":"127","author":"Eletto","year":"2014","journal-title":"J Cell Sci"},{"key":"key20200713162412_b50-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1016\/j.redox.2014.07.005","article-title":"Mitochondrial stress signaling in longevity: A new role for mitochondrial function in aging","volume":"2","author":"Hill","year":"2014","journal-title":"Redox Biol"},{"key":"key20200713162412_b51-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1126\/science.1124646","article-title":"Opposing activities protect against age-onset proteotoxicity","volume":"313","author":"Cohen","year":"2006","journal-title":"Science"},{"key":"key20200713162412_b52-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"e1004019","DOI":"10.1371\/journal.pgen.1004019","article-title":"Lifespan extension conferred by endoplasmic reticulum secretory pathway deficiency requires induction of the unfolded protein response","volume":"10","author":"Labunskyy","year":"2014","journal-title":"PLoS Genet"},{"key":"key20200713162412_b53-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"358","DOI":"10.2174\/157340608784872299","article-title":"Metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes","volume":"4","author":"Correia","year":"2008","journal-title":"Med Chem"},{"key":"key20200713162412_b54-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"16839","DOI":"10.1038\/srep16839","article-title":"ERK2 mediates inner hair cell survival and decreases susceptibility to noise-induced hearing loss","volume":"5","author":"Kurioka","year":"2015","journal-title":"Sci Rep"},{"key":"key20200713162412_b55-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"3798","DOI":"10.1523\/JNEUROSCI.5338-05.2006","article-title":"Inhibition of apoptosis by P2Y2 receptor activation: Novel pathways for neuronal survival","volume":"26","author":"Arthur","year":"2006","journal-title":"J Neurosci"},{"key":"key20200713162412_b56-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1126\/science.270.5240.1326","article-title":"Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis","volume":"270","author":"Xia","year":"1995","journal-title":"Science"},{"key":"key20200713162412_b57-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"12200","DOI":"10.1074\/jbc.275.16.12200","article-title":"Persistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures","volume":"275","author":"Stanciu","year":"2000","journal-title":"J Biol Chem"},{"key":"key20200713162412_b58-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"11851","DOI":"10.1158\/0008-5472.CAN-06-1377","article-title":"Sorafenib blocks the RAF\/MEK\/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC\/PRF\/5","volume":"66","author":"Liu","year":"2006","journal-title":"Cancer Res"},{"key":"key20200713162412_b59-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3389\/fcimb.2017.00058","article-title":"Helicobacter pylori Secreted protein HP1286 triggers apoptosis in macrophages via TNF-independent and ERK MAPK-dependent pathways","volume":"7","author":"Tavares","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"key20200713162412_b60-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1038\/srep01814","article-title":"S-nitrosylation of ERK inhibits ERK phosphorylation and induces apoptosis","volume":"3","author":"Feng","year":"2013","journal-title":"Sci Rep"},{"key":"key20200713162412_b61-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jnutbio.2017.10.015","article-title":"Resveratrol and pinostilbene confer neuroprotection against aging-related deficits through an ERK1\/2-dependent mechanism","volume":"54","author":"Allen","year":"2018","journal-title":"J Nutr Biochem"},{"key":"key20200713162412_b62-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"B539","DOI":"10.1093\/gerona\/54.12.B539","article-title":"Age-associated impairment in brain MAPK signal pathways and the effect of caloric restriction in Fischer 344 rats","volume":"54","author":"Zhen","year":"1999","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"key20200713162412_b63-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1124\/jpet.106.107367","article-title":"A death-promoting role for extracellular signal-regulated kinase","volume":"319","author":"Zhuang","year":"2006","journal-title":"J Pharmacol Exp Ther"},{"key":"key20200713162412_b64-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"10962","DOI":"10.1074\/jbc.M312048200","article-title":"Inhibition of ligand-independent ERK1\/2 activity in kidney proximal tubular cells deprived of soluble survival factors up-regulates Akt and prevents apoptosis","volume":"279","author":"Sinha","year":"2004","journal-title":"J Biol Chem"},{"key":"key20200713162412_b65-ijmm-45-03-0715","doi-asserted-by":"publisher","first-page":"31099","DOI":"10.1074\/jbc.M111974200","article-title":"Regulation of Raf-Akt cross-talk","volume":"277","author":"Moelling","year":"2002","journal-title":"J Biol Chem"}],"container-title":["International Journal of Molecular Medicine"],"original-title":[],"deposited":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T03:33:38Z","timestamp":1613878418000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.spandidos-publications.com\/10.3892\/ijmm.2020.4453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,8]]},"references-count":65,"URL":"https:\/\/doi.org\/10.3892\/ijmm.2020.4453","relation":{},"ISSN":["1107-3756","1791-244X"],"issn-type":[{"value":"1107-3756","type":"print"},{"value":"1791-244X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,8]]}}}