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Inhibiting histone deacetylase 6 partly protects cultured rat cortical neurons from oxygenglucose deprivationinduced necroptosis

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Necroptosis has an important role in ischemiareperfusion damage. The expression of histone deacetylase 6 (HDAC6) is upregulated in neurons following ischemiareperfusion, however, whether HDAC6 is closely involved in the necroptosis, which occurs during ischemiareperfusion damage remains to be elucidated. In the present study, the roles of HDAC6 in the necroptosis of cultured rat cortical neurons were investigated in a oxygenglucose deprivation (OGD) model. The results demonstrated that OGD induced marked necroptosis of cultured rat cortical neurons and upregulated the expression of HDAC6 in the cultured neurons, compared with the control (P<0.05). The necroptosis inhibitor, necrostatin1 (Nec1), decreased The expression of HDAC6 in the OGDtreated cultured neurons, accompanied by the inhibition of necroptosis. Further investigation revealed that, compared with OGD treatment alone, inhibiting the activity of HDAC6 with tubacin, a specific HDAC6 inhibitor, reduced the OGDinduced necroptosis of the cultured rat cortical neurons (P<0.05), which was similar to the change following treatment with Nec1 (P>0.05). In addition, inhibiting the activity of HDAC6 reversed the OGDinduced increase of reactive oxygen species (ROS) and the OGDinduced decrease of acetylated tubulin in the cultured rat cortical neurons (P<0.05), compared with the neurons treated with OGD alone). The levels of acetylated tubulin in the cultured neurons following treatment with OGD and tubacin were significantly higher than those in the control (P<0.05). These results suggested that HDAC6 was involved in the necroptosis of neurons during ischemiareperfusion by modulating the levels of ROS and acetylated tubulin.
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Document Type: Research Article

Affiliations: 1: Department of Anatomy, Medical College of Hunan Normal University, Changsha, Hunan 410013, P.R. China 2: Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410000, P.R. China 3: Department of Nursing, Medical College of Hunan Normal University, Changsha, Hunan 410013, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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