{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:32:00Z","timestamp":1787765520143,"version":"build-2784847793"},"reference-count":35,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T00:00:00Z","timestamp":1550793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31801462"],"award-info":[{"award-number":["31801462"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005270","name":"Fujian Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2018J05063"],"award-info":[{"award-number":["2018J05063"]}],"id":[{"id":"10.13039\/501100005270","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003410","name":"Department of Education, Fujian Province","doi-asserted-by":"publisher","award":["JAT170502"],"award-info":[{"award-number":["JAT170502"]}],"id":[{"id":"10.13039\/501100003410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003410","name":"Department of Education, Fujian Province","doi-asserted-by":"publisher","award":["the Program for Outstanding Young Research Talents in Fujian Province University"],"award-info":[{"award-number":["the Program for Outstanding Young Research Talents in Fujian Province University"]}],"id":[{"id":"10.13039\/501100003410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009617","name":"Putian Science and Technology Bureau","doi-asserted-by":"publisher","award":["2017S3001"],"award-info":[{"award-number":["2017S3001"]}],"id":[{"id":"10.13039\/501100009617","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010614","name":"Putian University","doi-asserted-by":"publisher","award":["2017080"],"award-info":[{"award-number":["2017080"]}],"id":[{"id":"10.13039\/501100010614","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010614","name":"Putian University","doi-asserted-by":"publisher","award":["2018055"],"award-info":[{"award-number":["2018055"]}],"id":[{"id":"10.13039\/501100010614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The phosphorylation of histone H3 at serine 10 (p-H3S10) has been shown to be closely correlated with mitotic chromosome condensation. We previously reported that intracellular silver nanoparticles (AgNPs) release Ag ions that alter actin filament dynamics, leading to the activation of Aurora kinases and the formation of p-H3S10 through a mechanism clearly different from that occurring during mitosis. In the present study, we examined other mechanisms underlying the induction of p-H3S10 formation by AgNPs. We observed that the early formation of p-H3S10 induced by AgNPs occurred via the activation of mitogen-activated protein kinase (MAPK) pathways, specifically the Jun N-terminal protein kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways. The late AgNP-induced p-H3S10 formation occurred via the activation of the entire MAPK cascade. On the other hand, p-H3S10 formation was not due to DNA damage induced by AgNPs, or the activation of the kinases ataxia telangiectasia-mutated (ATM) and ATM-Rad3-related (ATR). Several studies have compared the mechanism of AgNP toxicity to a Trojan horse-type molecular pathway. We observed different effects of AgNO3 (Ag+) and AgNPs on cells, and only the JNK inhibitor suppressed the temporary AgNO3-induced formation of p-H3S10. These results strongly indicate that AgNP-induced p-H3S10 formation does not rely solely on one signaling pathway, but rather may involve two or more pathways.<\/jats:p>","DOI":"10.3390\/biom9020078","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T11:26:14Z","timestamp":1550834774000},"page":"78","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Silver Nanoparticle-Induced Phosphorylation of Histone H3 at Serine 10 Involves MAPK Pathways"],"prefix":"10.3390","volume":"9","author":[{"given":"Xiaoxu","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Environmental and Biological Engineering, Putian University, Putian 351100, China"},{"name":"Fujian Provincial Key Laboratory of Ecology-Toxicological Effects &amp; Control for Emerging Contaminants, Putian 351100, China"},{"name":"Key Laboratory of Ecological Environment and Information Atlas (Putian University) Fujian Provincial University, Putian 351100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanying","family":"Rao","sequence":"additional","affiliation":[{"name":"College of Environmental and Biological Engineering, Putian University, Putian 351100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Environmental and Biological Engineering, Putian University, Putian 351100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoukai","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Environmental and Biological Engineering, Putian University, Putian 351100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumei","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Environmental and Biological Engineering, Putian University, Putian 351100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangliang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Environmental and Biological Engineering, Putian University, Putian 351100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Environmental and Biological Engineering, Putian University, Putian 351100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/S1516-14392009000100002","article-title":"Nanocomposites: Synthesis, Structure, Properties and New Application Opportunities","volume":"12","author":"Satyanarayana","year":"2009","journal-title":"Mater. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1021\/es103316q","article-title":"120 Years of Nanosilver History: Implications for Policy Makers","volume":"45","author":"Nowack","year":"2011","journal-title":"Environ. Sci. Technol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Guo, H., Zhang, J., Boudreau, M., Meng, J., Yin, J.-J., Liu, J., and Xu, H. (2016). Intravenous administration of silver nanoparticles causes organ toxicity through intracellular ROS-related loss of inter-endothelial junction. Part. Fibre Toxicol., 13.","DOI":"10.1186\/s12989-016-0133-9"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.toxlet.2013.07.011","article-title":"Multi-platform genotoxicity analysis of silver nanoparticles in the model cell line CHO-K1","volume":"222","author":"Jiang","year":"2013","journal-title":"Toxicol. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.tiv.2009.06.001","article-title":"Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells","volume":"23","author":"Kim","year":"2009","journal-title":"Toxicol. In Vitro"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.toxlet.2012.07.009","article-title":"Cellular uptake, intracellular trafficking and cytotoxicity of silver nanoparticles","volume":"213","author":"Singh","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1002\/anie.201205923","article-title":"Silver as Antibacterial Agent: Ion, Nanoparticle, and Metal","volume":"52","author":"Chernousova","year":"2013","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2007.10.004","article-title":"Nanosilver: A nanoproduct in medical application","volume":"176","author":"Chen","year":"2008","journal-title":"Toxicol. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.tox.2008.09.007","article-title":"In vitro investigation of oxide nanoparticle and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes","volume":"253","author":"Gouget","year":"2008","journal-title":"Toxicology"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cho, J.-G., Kim, K.-T., Ryu, T.-K., Lee, J.-W., Kim, J.-E., Kim, J., Lee, B.-C., Jo, E.-H., Yoon, J., and Eom, I.-C. (2013). Stepwise Embryonic Toxicity of Silver Nanoparticles on Oryzias latipes. BioMed Res. Int.","DOI":"10.1155\/2013\/494671"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jphotobiol.2016.06.046","article-title":"Coexposure to silver nanoparticles and ultraviolet A synergistically enhances the phosphorylation of histone H2AX","volume":"162","author":"Zhao","year":"2016","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1034\/j.1600-065X.2003.00060.x","article-title":"The role of DNA breaks in genomic instability and tumorigenesis","volume":"194","author":"Mills","year":"2003","journal-title":"Immunol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/nrc2523","article-title":"OPINION gamma H2AX and cancer","volume":"8","author":"Bonner","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1007\/s12035-016-9688-6","article-title":"Prolonged Effects of Silver Nanoparticles on p53\/p21 Pathway-Mediated Proliferation, DNA Damage Response, and Methylation Parameters in HT22 Hippocampal Neuronal Cells","volume":"54","author":"Mytych","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5003","DOI":"10.1021\/acs.est.5b00542","article-title":"Evaluating the Toxicity of Silver Nanoparticles by Detecting Phosphorylation of Histone H3 in Combination with Flow Cytometry Side-Scattered Light","volume":"49","author":"Zhao","year":"2015","journal-title":"Environ. Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1007\/s004120050256","article-title":"Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation","volume":"106","author":"Hendzel","year":"1997","journal-title":"Chromosoma"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0092-8674(00)80718-7","article-title":"Phosphorylation of histone H3 is required for proper chromosome condensation and segregation","volume":"97","author":"Wei","year":"1999","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5818","DOI":"10.1158\/0008-5472.CAN-05-0197","article-title":"Phosphorylation of histone H3 at serine 10 is indispensable for neoplastic cell transformation","volume":"65","author":"Choi","year":"2005","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1158\/0008-5472.CAN-07-6597","article-title":"Mitogen- and stress-activated kinase 1-mediated histone H3 phosphorylation is crucial for cell transformation","volume":"68","author":"Kim","year":"2008","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13183","DOI":"10.1074\/jbc.M300269200","article-title":"Tumor promoter arsenite stimulates histone H3 phosphoacetylation of proto-oncogenes c-fos and c-jun chromatin in human diploid fibroblasts","volume":"278","author":"Li","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1093\/carcin\/bgn084","article-title":"Nickel compounds induce phosphorylation of histone H3 at serine 10 by activating JNK-MAPK pathway","volume":"29","author":"Ke","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/onc.2012.71","article-title":"UVB-induced COX-2 expression requires histone H3 phosphorylation at Ser10 and Ser28","volume":"32","author":"Keum","year":"2013","journal-title":"Oncogene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1093\/carcin\/bgt492","article-title":"Cigarette sidestream smoke induces histone H3 phosphorylation via JNK and PI3K\/Akt pathways, leading to the expression of proto-oncogenes","volume":"35","author":"Ibuki","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.toxlet.2017.05.009","article-title":"Silver nanoparticle-induced phosphorylation of histone H3 at serine 10 is due to dynamic changes in actin filaments and the activation of Aurora kinases","volume":"276","author":"Zhao","year":"2017","journal-title":"Toxicol. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7629","DOI":"10.1021\/es300433x","article-title":"Flow Cytometric Evaluation of Nanoparticles Using Side-Scattered Light and Reactive Oxygen Species-Mediated Fluorescence-Correlation with Genotoxicity","volume":"46","author":"Toduka","year":"2012","journal-title":"Environ. Sci. Technol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ejphar.2007.06.049","article-title":"Histone H3 phosphorylation at serine 10 and serine 28 is mediated by p38 MAPK in rat hepatocytes exposed to ethanol and acetaldehyde","volume":"573","author":"Lee","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3650","DOI":"10.1038\/onc.2010.129","article-title":"Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate","volume":"29","author":"Liu","year":"2010","journal-title":"Oncogene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.mrrev.2004.06.004","article-title":"Genotoxicity of environmental tobacco smoke: A review","volume":"567","year":"2004","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31932","DOI":"10.1074\/jbc.M111.267633","article-title":"Cigarette Smoke Induces Akt Protein Degradation by the Ubiquitin-Proteasome System","volume":"286","author":"Kim","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8337","DOI":"10.1021\/es1020668","article-title":"p38 MAPK Activation, DNA Damage, Cell Cycle Arrest and Apoptosis as Mechanisms of Toxicity of Silver Nanoparticles in Jurkat T Cells","volume":"44","author":"Eom","year":"2010","journal-title":"Environ. Sci. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00013.2003","article-title":"Functional diversity of protein phosphatase-1, a cellular economizer and reset button","volume":"84","author":"Ceulemans","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.tiv.2009.12.001","article-title":"Silver nanoparticles induce cytotoxicity by a Trojan-horse type mechanism","volume":"24","author":"Park","year":"2010","journal-title":"Toxicol. In Vitro"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.scitotenv.2013.03.098","article-title":"Synergistic bactericidal effect by combined exposure to Ag nanoparticles and UVA","volume":"458","author":"Zhao","year":"2013","journal-title":"Sci. Total Environ."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s00775-007-0208-z","article-title":"Silver nanoparticles: Partial oxidation and antibacterial activities","volume":"12","author":"Lok","year":"2007","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_35","first-page":"2191","article-title":"Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures","volume":"10","author":"Murugan","year":"2015","journal-title":"Int. J. Nanomed."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/2\/78\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:34:12Z","timestamp":1760186052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/2\/78"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,22]]},"references-count":35,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["biom9020078"],"URL":"https:\/\/doi.org\/10.3390\/biom9020078","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,22]]}}}