Inhibiting histone deacetylase 6 partly protects cultured rat cortical neurons from oxygen‑glucose deprivation‑induced necroptosis

Yuan,Liming; Wang,Zhen; Liu,Lihua; Jian,Xiaohong

doi:10.3892/mmr.2015.3779

Inhibiting histone deacetylase 6 partly protects cultured rat cortical neurons from oxygen‑glucose deprivation‑induced necroptosis

Authors:
- Liming Yuan
- Zhen Wang
- Lihua Liu
- Xiaohong Jian
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Affiliations: Department of Anatomy, Medical College of Hunan Normal University, Changsha, Hunan 410013, P.R. China, Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410000, P.R. China, Department of Nursing, Medical College of Hunan Normal University, Changsha, Hunan 410013, P.R. China
Published online on: May 13, 2015 https://doi.org/10.3892/mmr.2015.3779
Pages: 2661-2667
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Necroptosis has an important role in ischemia‑reperfusion damage. The expression of histone deacetylase 6 (HDAC6) is upregulated in neurons following ischemia‑reperfusion, however, whether HDAC6 is closely involved in the necroptosis, which occurs during ischemia‑reperfusion 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 oxygen‑glucose 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, necrostatin‑1 (Nec‑1), decreased The expression of HDAC6 in the OGD‑treated 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 OGD‑induced necroptosis of the cultured rat cortical neurons (P<0.05), which was similar to the change following treatment with Nec‑1 (P>0.05). In addition, inhibiting the activity of HDAC6 reversed the OGD‑induced increase of reactive oxygen species (ROS) and the OGD‑induced 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 ischemia‑reperfusion by modulating the levels of ROS and acetylated tubulin.

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