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HDAC2 inhibitor CAY10683 reduces intestinal epithelial cell apoptosis by inhibiting mitochondrial apoptosis pathway in acute liver failure

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dc.contributor.authorLiu, Yang
dc.contributor.authorWang, Yao
dc.contributor.authorChen, Qian
dc.contributor.authorJiao, Fangzhou
dc.contributor.authorWang, Luwen
dc.contributor.authorGong, Zuojiong
dc.date.accessioned2022-10-20T08:58:25Z
dc.date.available2022-10-20T08:58:25Z
dc.date.issued2019
dc.description.abstractIntroduction. Histone deacetylases (HDAC) inhibitor has the effect of anti-tumor and inhibiting apoptosis, and could inhibit the release of inflammatory factors, reducing the damage to liver and enterocytes in acute liver failure (ALF). HDAC2 specific inhibitor CAY10683 was used to verify the protective effect on acute liver failure through reducing intestinal epithelial cell apoptosis by inhibiting mitochondrial apoptosis pathway. Materials and methods. Lipopolysaccharide/D- galactosamine (LPS/D-GalN) was used to induce ALF in Sprague-Dawley rats. A total of 18 healthy rats were randomly divided into three groups. Rats in ALF group and CAY10683 group were given the same amount of normal sodium or CAY10683 2 hours before ALF model protocol was conducted. NCM460 cells were given LPS/D-GalN to establish an apoptotic model. Flow cytometry analysis was used to determine the apoptosis of enterocytes, and TUNEL assay was used to observe the apoptosis of NCM460 cells. The expression of bax was observed by immunofluorescence. The expression of histone proteins, HDAC2 and molecules in the apoptotic signaling pathway were determined by Western blotting and real-time PCR. Results. CAY10683 improves histological and functional changes in ALF model. Compared with control group, LPS/D-GalN induced massive apoptosis of rat intestinal tissues and NCM460 cells (P<0.05), and the apoptosis rate was significantly reduced after CAY10683 treatment (P<0.05). The expression of bax was increased significantly in the model groups (P<0.05), and reduced with the treatment of CAY10683 (P<0.05). Compared with the model group, CAY10683 inhibits mitochondrial apoptosis in intestinal tissues and NCM460 cells (P<0.05). Conclusion. CAY10683 reduces the damage to liver and intestinal tissue, and plays an important role in inhibiting mitochondrial apoptosis in ALF rats and in NCM460 cellses
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dc.format.extent12es
dc.identifier.citationHistology and Histopathology Vol. 34, nº 10 (2019)
dc.identifier.doihttps://doi.org/10.14670/HH-18-120
dc.identifier.issn0213-3911
dc.identifier.issn1699-5848
dc.identifier.urihttp://hdl.handle.net/10201/124706
dc.languageenges
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologia
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHistone acetylase inhibitores
dc.subjectCAY10683es
dc.subjectMitochondrial apoptosises
dc.subjectEnterocytees
dc.subjectAcute liver failurees
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleHDAC2 inhibitor CAY10683 reduces intestinal epithelial cell apoptosis by inhibiting mitochondrial apoptosis pathway in acute liver failurees
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.34,nº10 (2019)