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IR@PKUHSC  > 北京大学第一临床医学院  > 呼吸和危重症医学科  > 期刊论文
学科主题: 临床医学
题名:
C/EBP Homologous Binding Protein (CHOP) Underlies Neural Injury in Sleep Apnea Model
作者: Chou, Yu-Ting1,2,3,4; Zhan, Guanxia5; Zhu, Yan5; Fenik, Polina5; Panossian, Lori5,6; Li, YanPeng5; Zhang, Jing7; Veasey, Sigrid5,6
关键词: Hypoxia ; reoxygenation ; unfolded protein response ; PERK ; GADD153 and gp91(phox)
刊名: SLEEP
发表日期: 2013-04-01
DOI: 10.5665/sleep.2528
卷: 36, 期:4, 页:481-492
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Clinical Neurology ; Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: ENDOPLASMIC-RETICULUM STRESS ; TERM INTERMITTENT HYPOXIA ; UPPER AIRWAY MUSCLE ; NADPH OXIDASE ; OXIDATIVE STRESS ; CHOLINE-ACETYLTRANSFERASE ; NEURONAL DEATH ; MURINE MODEL ; DISORDERS ; MICE
英文摘要:

Study Objectives: Obstructive sleep apnea (OSA) is associated with cognitive impairment and neuronal injury. Long-term exposure to intermittent hypoxia (LTIH) in rodents, modeling the oxygenation patterns in sleep apnea, results in NADPH oxidase 2 (Nox2) oxidative injury to many neuronal populations. Brainstem motoneurons susceptible to LTIH injury show uncompensated endoplasmic reticulum stress responses with increased (CCAAT/enhancer binding protein homologous protein (CHOP). We hypothesized that CHOP underlies LTIH oxidative injury. In this series of studies, we first determined whether CHOP is upregulated in other brain regions susceptible to LTIH oxidative Nox2 injury and then determined whether CHOP plays an adaptive or injurious role in the LTIH response. To integrate these findings with previous studies examining LTIH neural injury, we examined the role of CHOP in Nox2, hypoxia-inducible factor-1 alpha (HIF-1 alpha) responses, oxidative injury and apoptosis, and neuron loss.

Design: Within/between mice subjects.

Setting: Laboratory setting.

Participants/Subjects: CHOP null and wild-type adult male mice.

Interventions: LTIH or sham LTIH.

Measurements and Main Results: Relative to wild-type mice, CHOP-/- mice conferred resistance to oxidative stress (superoxide production/carbonyl proteins) in brain regions examined: cortex, hippocampus, and motor nuclei. CHOP deletion prevented LTIH upregulation of Nox2 and HIF-1 alpha in the hippocampus, cortex, and brainstem motoneurons and protected mice from neuronal apoptosis and motoneuron loss.

Conclusions: Endogenous CHOP is necessary for LTIH-induced HIF-1 alpha, Nox2 upregulation, and oxidative stress; CHOP influences LTIH-induced apoptosis in neurons and loss of neurons. Findings support the concept that minimizing CHOP may provide neuroprotection in OSA.

语种: 英语
所属项目编号: HL079555 ; HL096037
项目资助者: NIH HLBI
WOS记录号: WOS:000316939000007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65803
Appears in Collections:北京大学第一临床医学院_呼吸和危重症医学科_期刊论文

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作者单位: 1.Chang Gung Mem Hosp, Sleep Ctr, Chiayi, Taiwan
2.Chang Gung Mem Hosp, Dept Pulm & Crit Care Med, Chiayi, Taiwan
3.Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Tao Yuan, Taiwan
4.Chang Gung Univ Sci & Technol, Tao Yuan, Taiwan
5.Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA
6.Univ Penn, Sch Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA
7.Peking Univ, Hosp 1, Dept Pulm Med, Beijing 100871, Peoples R China

Recommended Citation:
Chou, Yu-Ting,Zhan, Guanxia,Zhu, Yan,et al. C/EBP Homologous Binding Protein (CHOP) Underlies Neural Injury in Sleep Apnea Model[J]. SLEEP,2013,36(4):481-492.
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