title: Downregulation of NAD-Dependent Deacetylase SIRT2 Protects Mouse Brain Against Ischemic Stroke.
abstract: Sirtuin 2 (SIRT2) is a member of NAD+-dependent protein deacetylases involved in a wide range of pathophysiological processes including myocardial injury, Parkinson's disease, and Huntington's disease. However, the direct implication of SIRT2 in ischemic stroke is still unclear. In the present study, we observed that SIRT2 protein was mainly expressed in the cytoplasm of neurons, but not in astrocyte and microglia. SIRT2 was upregulated in ischemic neurons in the oxygen-glucose deprivation cell model and in the transient middle cerebral artery occlusion (tMCAo) mouse model. Moreover, expression of SIRT2 was evaluated by immunohistochemistry in human brains consisting of ischemic penumbra of cerebral stroke, and their age-matched normal controls without diagnosed neurological disorders. The results revealed that SIRT2 was mainly expressed in the cytoplasm and neurites of neurons in the brains of normal subjects, while an elevated expression and nuclear translocation of SIRT2 were detected in the ischemic penumbra of cerebral stroke. Downregulation of SIRT2 using the SIRT2-specific inhibitor AGK2 or SIRT2 knockout had neuroprotective effects in tMCAo model, which could decrease the infract volume and neurological impairment scores. In summary, our findings revealed that SIRT2 was upregulated during neuronal ischemia and translocated into neuronal nuclei, while downregulation of SIRT2 could significantly protect neurons against cerebral ischemia.
authors: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People's Republic of China.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People's Republic of China.|Key Laboratory of Neurological Diseases, Ministry of Education, Hubei Provincial Key Laboratory of Neurological Diseases, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors: Xiao Qiang
authors: XQ
authors: Xie
authors: Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People's Republic of China.|Key Laboratory of Neurological Diseases, Ministry of Education, Hubei Provincial Key Laboratory of Neurological Diseases, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.|Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People's Republic of China.
authors: Pei
authors: P
authors: Zhang
authors: Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People's Republic of China. tianbo@mails.tjmu.edu.cn.|Key Laboratory of Neurological Diseases, Ministry of Education, Hubei Provincial Key Laboratory of Neurological Diseases, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. tianbo@mails.tjmu.edu.cn.|Department of Neurobiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People's Republic of China. tianbo@mails.tjmu.edu.cn.
authors: Bo
authors: B
authors: Tian
authors: Department of Pathophysiology, School of Basic Medicine, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People's Republic of China. chenxq@mails.tjmu.edu.cn.|Institute for Brain Research, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, People's Republic of China. chenxq@mails.tjmu.edu.cn.|Key Laboratory of Neurological Diseases, Ministry of Education, Hubei Provincial Key Laboratory of Neurological Diseases, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. chenxq@mails.tjmu.edu.cn.
authors: Xiao Qian
authors: http://orcid.org/0000-0002-2673-2977
authors: XQ
authors: Chen
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D056565:Sirtuin 2 / Q000172:deficiency*; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
chemical_list: C418743:Sirt2 protein, mouse; D056565:Sirtuin 2
keywords: AGK2; Ischemic stroke; Middle cerebral artery occlusion; Neuron; SIRT2