Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro
Background. A substantial increase in histone deacetylase 3 (HDAC3) expression is implicated in the pathological process of diabetes and stroke. However, it is unclear whether HDAC3 plays an important role in diabetes complicated with stroke. We aimed to explore the role and the potential mechanisms...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2019/8520856 |
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| author | Bo Zhao Quan Yuan Jia-bao Hou Zhong-yuan Xia Li-ying Zhan Mei Li Meng Jiang Wen-wei Gao Lian Liu |
| author_facet | Bo Zhao Quan Yuan Jia-bao Hou Zhong-yuan Xia Li-ying Zhan Mei Li Meng Jiang Wen-wei Gao Lian Liu |
| author_sort | Bo Zhao |
| collection | DOAJ |
| description | Background. A substantial increase in histone deacetylase 3 (HDAC3) expression is implicated in the pathological process of diabetes and stroke. However, it is unclear whether HDAC3 plays an important role in diabetes complicated with stroke. We aimed to explore the role and the potential mechanisms of HDAC3 in cerebral ischemia/reperfusion (I/R) injury in diabetic state. Methods. Diabetic mice were subjected to 1 h ischemia, followed by 24 h reperfusion. PC12 cells were exposed to high glucose for 24 h, followed by 3 h of hypoxia and 6 h of reoxygenation (H/R). Diabetic mice received RGFP966 (the specific HDAC3 inhibitor) or vehicle 30 minutes before the middle cerebral artery occlusion (MCAO), and high glucose-incubated PC12 cells were pretreated with RGFP966 or vehicle 6 h before H/R. Results. HDAC3 inhibition reduced the cerebral infarct volume, ameliorated pathological changes, improved the cell viability and cytotoxicity, alleviated apoptosis, attenuated oxidative stress, and enhanced autophagy in cerebral I/R injury model in diabetic state in vivo and in vitro. Furthermore, we found that the expression of HDAC3 was remarkably amplified, and the Bmal1 expression was notably decreased in diabetic mice with cerebral I/R, whereas this phenomenon was obviously reversed by RGFP966 pretreatment. Conclusions. These results suggested that the HDAC3 was involved in the pathological process of the complex disease of diabetic stroke. Suppression of HDAC3 exerted protective effects against cerebral I/R injury in diabetic state in vivo and in vitro via the modulation of oxidative stress, apoptosis, and autophagy, which might be mediated by the upregulation of Bmal1. |
| format | Article |
| id | doaj-art-7cd00c048f7e46c1ae8d94a3bab68e10 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-7cd00c048f7e46c1ae8d94a3bab68e102025-08-20T03:35:28ZengWileyJournal of Diabetes Research2314-67452314-67532019-01-01201910.1155/2019/85208568520856Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In VitroBo Zhao0Quan Yuan1Jia-bao Hou2Zhong-yuan Xia3Li-ying Zhan4Mei Li5Meng Jiang6Wen-wei Gao7Lian Liu8Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, ChinaDepartment of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, ChinaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province 430060, ChinaBackground. A substantial increase in histone deacetylase 3 (HDAC3) expression is implicated in the pathological process of diabetes and stroke. However, it is unclear whether HDAC3 plays an important role in diabetes complicated with stroke. We aimed to explore the role and the potential mechanisms of HDAC3 in cerebral ischemia/reperfusion (I/R) injury in diabetic state. Methods. Diabetic mice were subjected to 1 h ischemia, followed by 24 h reperfusion. PC12 cells were exposed to high glucose for 24 h, followed by 3 h of hypoxia and 6 h of reoxygenation (H/R). Diabetic mice received RGFP966 (the specific HDAC3 inhibitor) or vehicle 30 minutes before the middle cerebral artery occlusion (MCAO), and high glucose-incubated PC12 cells were pretreated with RGFP966 or vehicle 6 h before H/R. Results. HDAC3 inhibition reduced the cerebral infarct volume, ameliorated pathological changes, improved the cell viability and cytotoxicity, alleviated apoptosis, attenuated oxidative stress, and enhanced autophagy in cerebral I/R injury model in diabetic state in vivo and in vitro. Furthermore, we found that the expression of HDAC3 was remarkably amplified, and the Bmal1 expression was notably decreased in diabetic mice with cerebral I/R, whereas this phenomenon was obviously reversed by RGFP966 pretreatment. Conclusions. These results suggested that the HDAC3 was involved in the pathological process of the complex disease of diabetic stroke. Suppression of HDAC3 exerted protective effects against cerebral I/R injury in diabetic state in vivo and in vitro via the modulation of oxidative stress, apoptosis, and autophagy, which might be mediated by the upregulation of Bmal1.http://dx.doi.org/10.1155/2019/8520856 |
| spellingShingle | Bo Zhao Quan Yuan Jia-bao Hou Zhong-yuan Xia Li-ying Zhan Mei Li Meng Jiang Wen-wei Gao Lian Liu Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro Journal of Diabetes Research |
| title | Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro |
| title_full | Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro |
| title_fullStr | Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro |
| title_full_unstemmed | Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro |
| title_short | Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro |
| title_sort | inhibition of hdac3 ameliorates cerebral ischemia reperfusion injury in diabetic mice in vivo and in vitro |
| url | http://dx.doi.org/10.1155/2019/8520856 |
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