Neuroprotective mechanism of TMP269, a selective class IIA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury
TMP269 is a selective class IIA histone deacetylase inhibitor that has a protective effect on the central nervous system, whose specific mechanism of action is unclear. We aimed to reveal the optimal concentration of TMP269 for protecting against cerebral ischemia/reperfusion injury and its neuropro...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2020-01-01
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| Series: | Neural Regeneration Research |
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| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=2;spage=277;epage=284;aulast=Su |
| _version_ | 1818249751691264000 |
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| author | Lu Su Dan Liang Shen-Yi Kuang Qiang Dong Xiang Han Zheng Wang |
| author_facet | Lu Su Dan Liang Shen-Yi Kuang Qiang Dong Xiang Han Zheng Wang |
| author_sort | Lu Su |
| collection | DOAJ |
| description | TMP269 is a selective class IIA histone deacetylase inhibitor that has a protective effect on the central nervous system, whose specific mechanism of action is unclear. We aimed to reveal the optimal concentration of TMP269 for protecting against cerebral ischemia/reperfusion injury and its neuroprotective mechanism. Male Sprague-Dawley rats were randomly divided into sham, ischemia/reperfusion, and 1, 4, 10 and 16 mg/kg TMP269 groups. Cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. TMP269 was intraperitoneally administered at different doses 0.5 hours before ischemia induction. Western blot assay and immunohistochemistry were used to detect effects of TMP269 on histone 2 acetylation. The results showed that the level of histone 2 acetylation was increased 24 hours after TMP269 injection. 2,3,5-Triphenyltetrazolium chloride staining was utilized to examine effect of TMP269 on infarct volume. The results found that different doses of TMP269 could reduce the infarct volume. Western blot assay, immunohistochemistry and Evans blue staining were employed to measure the effect of TMP269 on blood-brain barrier. The results showed that TMP269 counteracted the abnormal endothelial cell permeability changes caused by cerebral ischemia/reperfusion. Western blot assay and immunohistochemistry were used to determine the effect of TMP269 on tissue kallikrein. The results found that TMP269 up-regulated the expression of tissue kallikrein. Western blot assay further determined the optimal concentration to be 4 mg/kg. In conclusion, TMP269 plays a neuroprotective role by up-regulating the level of histone 2 acetylation, alleviating endothelial cell injury after cerebral ischemia/reperfusion, and up-regulating the expression of tissue kallikrein. The experimental protocol was approved in 2014 by the Department of Laboratory Animal Science, Fudan University, China (approval No. 20140143C001). |
| first_indexed | 2024-12-12T15:41:28Z |
| format | Article |
| id | doaj.art-5c0badb6edfb4be8a2fd4e31ca3d246b |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-12T15:41:28Z |
| publishDate | 2020-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-5c0badb6edfb4be8a2fd4e31ca3d246b2022-12-22T00:19:54ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742020-01-0115227728410.4103/1673-5374.265562Neuroprotective mechanism of TMP269, a selective class IIA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injuryLu SuDan LiangShen-Yi KuangQiang DongXiang HanZheng WangTMP269 is a selective class IIA histone deacetylase inhibitor that has a protective effect on the central nervous system, whose specific mechanism of action is unclear. We aimed to reveal the optimal concentration of TMP269 for protecting against cerebral ischemia/reperfusion injury and its neuroprotective mechanism. Male Sprague-Dawley rats were randomly divided into sham, ischemia/reperfusion, and 1, 4, 10 and 16 mg/kg TMP269 groups. Cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. TMP269 was intraperitoneally administered at different doses 0.5 hours before ischemia induction. Western blot assay and immunohistochemistry were used to detect effects of TMP269 on histone 2 acetylation. The results showed that the level of histone 2 acetylation was increased 24 hours after TMP269 injection. 2,3,5-Triphenyltetrazolium chloride staining was utilized to examine effect of TMP269 on infarct volume. The results found that different doses of TMP269 could reduce the infarct volume. Western blot assay, immunohistochemistry and Evans blue staining were employed to measure the effect of TMP269 on blood-brain barrier. The results showed that TMP269 counteracted the abnormal endothelial cell permeability changes caused by cerebral ischemia/reperfusion. Western blot assay and immunohistochemistry were used to determine the effect of TMP269 on tissue kallikrein. The results found that TMP269 up-regulated the expression of tissue kallikrein. Western blot assay further determined the optimal concentration to be 4 mg/kg. In conclusion, TMP269 plays a neuroprotective role by up-regulating the level of histone 2 acetylation, alleviating endothelial cell injury after cerebral ischemia/reperfusion, and up-regulating the expression of tissue kallikrein. The experimental protocol was approved in 2014 by the Department of Laboratory Animal Science, Fudan University, China (approval No. 20140143C001).http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=2;spage=277;epage=284;aulast=Sublood-brain barrier; drug treatment; endothelial cell permeability; histone deacetylase inhibitor; neuroprotection; stroke; tissue kallikrein; TMP269 |
| spellingShingle | Lu Su Dan Liang Shen-Yi Kuang Qiang Dong Xiang Han Zheng Wang Neuroprotective mechanism of TMP269, a selective class IIA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury Neural Regeneration Research blood-brain barrier; drug treatment; endothelial cell permeability; histone deacetylase inhibitor; neuroprotection; stroke; tissue kallikrein; TMP269 |
| title | Neuroprotective mechanism of TMP269, a selective class IIA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury |
| title_full | Neuroprotective mechanism of TMP269, a selective class IIA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury |
| title_fullStr | Neuroprotective mechanism of TMP269, a selective class IIA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury |
| title_full_unstemmed | Neuroprotective mechanism of TMP269, a selective class IIA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury |
| title_short | Neuroprotective mechanism of TMP269, a selective class IIA histone deacetylase inhibitor, after cerebral ischemia/reperfusion injury |
| title_sort | neuroprotective mechanism of tmp269 a selective class iia histone deacetylase inhibitor after cerebral ischemia reperfusion injury |
| topic | blood-brain barrier; drug treatment; endothelial cell permeability; histone deacetylase inhibitor; neuroprotection; stroke; tissue kallikrein; TMP269 |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=2;spage=277;epage=284;aulast=Su |
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