CD28 Deficiency Ameliorates Thoracic Blast Exposure-Induced Oxidative Stress and Apoptosis in the Brain through the PI3K/Nrf2/Keap1 Signaling Pathway

doi:10.1155/2019/8460290

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	CD28 Deficiency Ameliorates Thoracic Blast Exposure-Induced Oxidative Stress and Apoptosis in the Brain through the PI3K/Nrf2/Keap1 Signaling Pathway
	Cong, Peifang 2,3; Tong, Changci 3; Liu, Ying 3; Shi, Lin 3; Shi, Xiuyun 3; Zhao, Yan 1; Xiao, Keshen 1; Jin, Hongxu 3; Liu, Yunen 3; Hou, Mingxiao 2
刊名	OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
	2019-12-04
卷号	2019 页码:14
ISSN号	1942-0900
DOI	10.1155/2019/8460290
通讯作者	Liu, Yunen(lye9901@163.com) ; Hou, Mingxiao(houmingxiao188@163.com)
英文摘要	Blast exposure is a worldwide public health concern, but most related research has been focused on direct injury. Thoracic blast exposure-induced neurotrauma is a type of indirect injuries where research is lacking. As CD28 stimulates T cell activation and survival and contributes to inflammation initiation, it may play a role in thoracic blast exposure-induced neurotrauma. However, it has not been investigated. To explore the effects of CD28 on thoracic blast exposure-induced brain injury and its potential molecular mechanisms, a mouse model of thoracic blast exposure-induced brain injury was established. Fifty C57BL/6 wild-type (WT) and fifty CD28 knockout (CD28(-/-)) mice were randomly divided into five groups (one control group and four model groups), with ten mice (from each of the two models) for each group. Lung and brain tissue and serum samples were collected at 12 h, 24 h, 48 h, and 1 week after thoracic blast exposure. Histopathological changes were detected by hematoxylin-eosin staining. The expressions of inflammatory-related factors were detected by ELISA. Oxidative stress in the brain tissue was evaluated by determining the generation of reactive oxygen species (ROS) and the expressions of thioredoxin (TRX), malondialdehyde (MDA), SOD-1, and SOD-2. Apoptosis in the brain tissue was evaluated by TUNEL staining and the levels of Bax, Bcl-xL, Bad, Cytochrome C, and caspase-3. In addition, proteins of related pathways were also studied by western blotting and immunofluorescence. We found that CD28 deficiency significantly reduced thoracic blast exposure-induced histopathological changes and decreased the levels of inflammatory-related factors, including IL-1 beta, TNF-alpha, and S100 beta. In the brain tissue, CD28 deficiency also significantly attenuated thoracic blast exposure-induced generation of ROS and expressions of MDA, TRX, SOD-1, and SOD-2; lowered the number of apoptotic cells and the expression of Bax, cleaved caspase-3, Cytochrome C, and Bad; and maintained Bcl-xL expression. Additionally, CD28 deficiency significantly ameliorated thoracic blast exposure-induced increases of p-PI3K and Keap1 and the decrease of Nrf2 expression in the brain. Our results indicate that CD28 deficiency has a protective effect on thoracic blast exposure-induced brain injury that might be associated with the PI3K/Nrf2/Keap1 signaling pathway.
资助项目	Liaoning Province Key Scientific and Technological Project[201602774] ; Liaoning Province Key Scientific and Technological Project[20170540947] ; Liaoning Province Key Scientific and Technological Project[20180540045] ; PLA foundation of China[CSY12J002] ; PLA foundation of China[AWS14L008] ; PLA foundation of China[CSY13J003] ; Edanz Group China
WOS研究方向	Cell Biology
语种	英语
出版者	HINDAWI LTD
WOS记录号	WOS:000503779300005
资助机构	Liaoning Province Key Scientific and Technological Project ; PLA foundation of China ; Edanz Group China
内容类型	期刊论文
源URL	[http://ir.imr.ac.cn/handle/321006/136438]
专题	金属研究所_中国科学院金属研究所
通讯作者	Liu, Yunen; Hou, Mingxiao
作者单位	1.Chinese Acad Sci, Inst Met Res, 72 Wenhua Rd, Shenyang 110016, Liaoning, Peoples R China 2.Northeastern Univ, Coll Med & Biol Informat Engn, 195 Chuangxin Rd, Shenyang 110016, Liaoning, Peoples R China 3.Gen Hosp Northern Theater Command, Emergency Med Deptauma, Lab Rescue Ctr Severe Wound & Trauma PLA, 83 Wenhua Rd, Shenyang 110016, Liaoning, Peoples R China
推荐引用方式 GB/T 7714	Cong, Peifang,Tong, Changci,Liu, Ying,et al. CD28 Deficiency Ameliorates Thoracic Blast Exposure-Induced Oxidative Stress and Apoptosis in the Brain through the PI3K/Nrf2/Keap1 Signaling Pathway[J]. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY,2019,2019:14.
APA	Cong, Peifang.,Tong, Changci.,Liu, Ying.,Shi, Lin.,Shi, Xiuyun.,...&Hou, Mingxiao.(2019).CD28 Deficiency Ameliorates Thoracic Blast Exposure-Induced Oxidative Stress and Apoptosis in the Brain through the PI3K/Nrf2/Keap1 Signaling Pathway.OXIDATIVE MEDICINE AND CELLULAR LONGEVITY,2019,14.
MLA	Cong, Peifang,et al."CD28 Deficiency Ameliorates Thoracic Blast Exposure-Induced Oxidative Stress and Apoptosis in the Brain through the PI3K/Nrf2/Keap1 Signaling Pathway".OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019(2019):14.