{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T05:20:52Z","timestamp":1772342452855,"version":"3.50.1"},"reference-count":56,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,3,6]],"date-time":"2016-03-06T00:00:00Z","timestamp":1457222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2010\/50015\u20106 (MLSM)"],"award-info":[{"award-number":["2010\/50015\u20106 (MLSM)"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2012\/03238\u20105(MBF)"],"award-info":[{"award-number":["2012\/03238\u20105(MBF)"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["475261\/2012\u20107(MLSM)"],"award-info":[{"award-number":["475261\/2012\u20107(MLSM)"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>Diabetes is a complex multifactorial disorder characterized by chronic hyperglycemia due to impaired insulin secretion. Recent observations suggest that the complexity of the disease cannot be entirely accounted for genetic predisposition and a compelling argument for an epigenetic component is rapidly emerging. The use of histone deacetylase inhibitor (HDACi) in clinical setting is an emerging area of investigation. In this study, we have aimed to understand and compare the response of hepatocyte chromatin to valproic acid (VPA) and trichostatin A (TSA) treatments under normoglycemic or hyperglycemic conditions to expand our knowledge about the consequences of HDACi treatment in a diabetes cell model. Under normoglycemic conditions, these treatments promoted chromatin remodeling, as assessed by image analysis and H3K9ac and H3K9me2 abundance. Simultaneously, H3K9ac marks shifted to the nuclear periphery accompanied by HP1 dissociation from the heterochromatin and a G1 cell cycle arrest. More striking changes in the cell cycle progression and mitotic ratios required drastic treatment. Under hyperglycemic conditions, high glucose per se promoted chromatin changes similar to those promoted by VPA and TSA. Nonetheless, these results were not intensified in cells treated with HDACis under hyperglycemic conditions. Despite the absence of morphological changes being promoted, HDACi treatment seems to confer a physiological meaning, ameliorating the cellular hyperglycemic state through reduction of glucose production. These observations allow us to conclude that the glucose level to which the hepatocytes are subjected affects how chromatin responds to HDACi and their action under high\u2010glucose environment might not reflect on chromatin remodeling. J. Cell. Physiol. 231: 2257\u20132265, 2016. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25343","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T09:43:19Z","timestamp":1455788599000},"page":"2257-2265","source":"Crossref","is-referenced-by-count":15,"title":["Differential Response of Human Hepatocyte Chromatin to HDAC Inhibitors as a Function of Microenvironmental Glucose Level"],"prefix":"10.1002","volume":"231","author":[{"given":"Marina Barreto","family":"Felisbino","sequence":"first","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biology University of Campinas (Unicamp) Campinas S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thiago","family":"Alves da Costa","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biology University of Campinas (Unicamp) Campinas S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Silvia Viccari","family":"Gatti","sequence":"additional","affiliation":[{"name":"Department of Genetics, Evolution and Bioagents, Institute of Biology University of Campinas (Unicamp) Campinas S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Luiza Silveira","family":"Mello","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Institute of Biology University of Campinas (Unicamp) Campinas S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.223453"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2008.951251"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02621"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05913"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.3.10542"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.292104"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00021"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1868-7083-4-5"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm500829b"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.00104.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029144"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24865"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.02.042"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.22102"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.559"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.220350"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.266254"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055074"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kve022"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-012-9380-9"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12121"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303936"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.34.1613"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(199808)20:8<615::AID-BIES4>3.0.CO;2-H"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.581439"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1003"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.052555"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2012.05747.x"},{"key":"e_1_2_6_30_1","first-page":"4231","article-title":"Trichostatin A, a histone deacetylase inhibitor, suppresses proliferation and promotes apoptosis of esophageal squamous cell lines","volume":"11","author":"Ma J","year":"2015","journal-title":"Mol Med Rep"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micron.2009.02.010"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M905410199"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2012.03.009"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000240247"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.883206"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2010.144"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.12085"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/371832"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kve199"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.5540007"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.168781.113"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.08.120"},{"key":"e_1_2_6_43_1","first-page":"255","article-title":"Glucose toxicity: The implications of hyperglycemia in the pathophysiology of diabetes mellitus","volume":"18","author":"Rossetti L","year":"1995","journal-title":"Clin Invest Med"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27323"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.305041"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/35055010"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400441"},{"key":"e_1_2_6_48_1","first-page":"109","article-title":"Histone deacetylase inhibitors induce growth inhibition, cell cycle arrest and apoptosis in human choriocarcinoma cells","volume":"21","author":"Takai N","year":"2008","journal-title":"Int J Mol Med"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01293"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00200.2010"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2011.05497.x"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0665-5"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu7095352"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E04-11-0997"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.01.187"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408149200"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2265"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.25343","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.25343","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T04:50:44Z","timestamp":1696395044000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.25343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,6]]},"references-count":56,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1002\/jcp.25343"],"URL":"https:\/\/doi.org\/10.1002\/jcp.25343","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,6]]}}}