title: Delayed treatment with NSC23766 in streptozotocin-induced diabetic rats ameliorates post-ischemic neuronal apoptosis through suppression of mitochondrial p53 translocation.
abstract: NSC23766, a specific inhibitor of Rac1, has recently been shown to protect against cerebral ischemic injury, although the effects of NSC23766 in a diabetic model have not been examined. Therefore, the aim of our study was to investigate if NSC23766 provided neuroprotection in streptozotocin-induced diabetic rats and to determine the potential mechanism through which NSC23766 works. Diabetic Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 90 min. NSC23766 (10 or 30 mg kg(-1)) or isotonic saline were administered intraperitoneally twice daily starting 24 h after cerebral ischemia, for three consecutive days. Cerebral infarct volume, neurological deficit scores, neuronal apoptosis, and the release of cytochrome c, as well as the generation of ROS and mitochondrial integrity, were evaluated 96 h after reperfusion. In addition, the mitochondrial translocation of p53 and the expression of p53-upregulated modulator of apoptosis (PUMA) in the mitochondria of the cerebral ischemic cortex were determined by western blotting. NSC23766 not only ameliorated post-ischemic neuronal apoptosis but also decreased cerebral ischemia-induced mitochondrial p53 translocation and the expression of PUMA in mitochondria in diabetic rats. Thus, our data indicate that NSC23766 has therapeutic potential against cerebral ischemic reperfusion injury and that NSC23766 significantly ameliorates neuronal apoptosis by suppressing mitochondrial p53 translocation in streptozotocin-induced diabetic rats.
authors: Department of Anesthesiology, Xiangya Hospital of Center South University, Changsha 410078, Hunan Province, China.
authors: Juan
authors: J
authors: Liao
authors: Department of Anesthesiology, Xiangya Hospital of Center South University, Changsha 410078, Hunan Province, China. Electronic address: bennydoctor@163.com.
authors: Zhi
authors: Z
authors: Ye
authors: Department of Emergency, Xiangya Hospital of Central South University, Changsha 410008, China.
authors: Guoqing
authors: G
authors: Huang
authors: Department of Anesthesiology, Xiangya Hospital of Center South University, Changsha 410078, Hunan Province, China.
authors: Chang
authors: C
authors: Xu
authors: Department of Anesthesiology, Xiangya Hospital of Center South University, Changsha 410078, Hunan Province, China.
authors: Qulian
authors: Q
authors: Guo
authors: Department of Anesthesiology, Xiangya Hospital of Center South University, Changsha 410078, Hunan Province, China.
authors: E
authors: E
authors: Wang
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D045304:Cytochromes c / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D051017:Apoptosis Regulatory Proteins; C533952:Bbc3 protein, rat; C487513:NSC 23766; D018696:Neuroprotective Agents; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c
keywords: Apoptosis; Cerebral ischemia; Diabetes; P53; Reactive oxygen species (ROS)